Difference between revisions of "Paper - The course of the blood flow through the fetal mammalian heart"

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Three Figures
 
Three Figures
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* Contribution no. 130. Submitted as one section of a thesis in partial fulfillment of the requirements of Northwestern University for the degree of Doctor of Philosophy.
  
 
==Introduction And Historical==
 
==Introduction And Historical==
 +
There is little exact information regarding the physiology of the fetal circulation in mammals. Two major problems present themselves: 1) the circulation of blood through the fetal heart; 2) the nature of placental exchange and the gaseous content of the maternal and fetal vessels. It is with the first of these problems that the ‘present report is concerned, Whereas the second will appear in a separate publication.
  
There is little exact information regarding the physiology
 
of the fetal circulation in mammals. Two major problems
 
present themselves: 1) the circulation of blood through the
 
fetal heart; 2) the nature of placental exchange and the gaseous content of the maternal and fetal vessels. It is with the
 
first of these problems that the ‘present report is concerned,
 
Whereas the second will appear in a separate publication.
 
  
The history of the dispute concerning the blood flow within
+
The history of the dispute concerning the blood flow within the fetal heart and its quantitative distribution dates from the beginning of the fourth century. It has been reviewed so thoroughly by Pohlman (’09 b) that only an outline and analysis of the more important phases are necessary.
the fetal heart and its quantitative distribution dates from
 
the beginning of the fourth century. It has been reviewed so
 
thoroughly by Pohlman (’09 b) that only an outline and
 
analysis of the more important phases are necessary.
 
  
1. Early discoveries
+
===1. Early discoveries===
 +
Galen (about 300 AD.) gave the first adequate description of the fetal heart. He described the foramen ovale and the ductus arteriosus and mentioned their fates after birth. He further commented on the remarkable provisions of nature in requiring but a small amount of blood to flow through the lungs before their respiratory function began. Wliile Galen’s account of the anatomy of the fetal heart was quite accurate, he reversed the course of the blood and described it as flowing from the aorta to the lungs by means of the ductus arteriosusi
  
Galen (about 300 AD.) gave the first adequate description
 
of the fetal heart. He described the foramen ovale and the
 
ductus arteriosus and mentioned their fates after birth. He
 
further commented on the remarkable provisions of nature
 
in requiring but a small amount of blood to flow through
 
the lungs before their respiratory function began. Wliile
 
Galen’s account of the anatomy of the fetal heart was quite
 
  
1 Contribution no. 130. Submitted as one section of a thesis in partial fulfillment of the requirements of Northwestern University for the degree of Doctor
+
At this time there was much mystery concerning the adult circulation, and Galen further erred in assuming that the blood somehow passed through, the ventricular septum on its course from the right ventricle to the left. Vesalius (1543), some time later, rightly questioned the teachings of Galen on this point.
of Philosophy.
 
  
  
accurate, he reversed the course of the blood and described it
+
Servetus (1553) made the important discovery that the blood, after passing through the lungs, is of a bright red color. It is possible that he might have interpreted this observation in terms of the pulmonary and systemic circulations had it not been for his untimely death at the stake as a penalty for his alleged radical teachings. Servetus also recognized the foramen ovalein the fetal heart.
as flowing from the aorta to the lungs by means of the ductus
 
arteriosusi
 
  
At this time there was much mystery concerning the adult
+
===2. The Wolff-Ziegenspeck School===
circulation, and Galen further erred in assuming that the
+
In the middle of the eighteenth century, Wolff (1778; Pohlman, ’09 b, pp. 79, 80) thought he had found a new anatomical relationship between theforamen ovale and the inferior Vena cava. He pictured the inferior Vena cava entering the two atria on their posterior walls so that the limbus of the foramen ovale cut the caval orifice into two openings. On the basis of these relations, he taught that the inferior caval blood stream was split, half going to each atrium, and the effect being the same as if there were, indeed, two inferior venae cavae, one to each atrium. This conception means that the pulmonary return must equal the superior caval return, otherwise the circulation would be unbalanced.
blood somehow passed through, the ventricular septum on
 
its course from the right ventricle to the left. Vesalius
 
(1543), some time later, rightly questioned the teachings of
 
Galen on this point.
 
  
Servetus (1553) made the important discovery that the
+
Ziegenspeck.(’81, ’05) corroborated Wolff’s findings and likewise believed that the inferior caval stream was divided by the limbus of the foramen ovale. The following diagram represents Pohlman’s (’09 b, pp. 88, 89) quantitative interpretation of Ziegenspeck’s views:
blood, after passing through the lungs, is of a bright red
 
color. It is possible that he might have interpreted this
 
observation in terms of the pulmonary and systemic circulations had it not been for his untimely death at the stake as
 
a penalty for his alleged radical teachings. Servetus also
 
recognized the foramen ovalein the fetal heart.
 
  
2. The W0lfi”—Zt'egenspeck School
+
Lungs &———-——-————%—> Pulmonary return i
  
In the middle ‘ of the eighteenth century, VVolff (1778;
 
Pohlman, ’09 b, pp. 79, 80) thought he had found a new
 
anatomical relationship between theforamen ovale and the
 
inferior Vena cava. He pictured the inferior Vena cava entering the two atria on their posterior walls so that the limbus
 
of the foramen ovale cut the caval orifice into two openings.
 
On the basis of these relations, he taught that the inferior
 
caval blood stream was split, half going to each atrium, and
 
the effect being the same as if there were, indeed, two inferior
 
venae cavae, one to each atrium. This conception means that
 
the pulmonary return must equal the superior caval return,
 
otherwise the circulation would be unbalanced.
 
  
Ziegenspe-ck.(’81, ’05) corroborated Wolff’s findings and
+
Right ventricle 1} Left ventricle 1} . \ /, Ductus arteriosus } Left atrium i \- /' Aorta descendens %—————-——>‘ Vena cava inferior §
likewise believed that the inferior caval stream was divided
 
by the limbus of the foramen ovale. The following diagram
 
represents Pohlman’s (’09 b, pp. 88, 89) quantitative interpretation of Ziegenspeck’s views:
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 445
 
  
Lungs &———-——-————%—> Pulmonary return i
 
  
/' \.
+
Pars communis aortae & Right atrium
Right ventricle 1} Left ventricle 1}
 
. \ /,
 
Ductus arteriosus } Left atrium i
 
\- /'
 
Aorta descendens %—————-——>‘ Vena cava inferior §
 
 
 
/' \
 
 
 
Pars communis aortae & Right atrium %;
 
/' \- ‘
 
  
 
Left ventricle 1} Right ventricle %
 
Left ventricle 1} Right ventricle %
 
\- /'
 
  
 
Aa. carotis et subclavius :} —-> Vena cava superior
 
Aa. carotis et subclavius :} —-> Vena cava superior
  
These deductions were based upon a series of thirty—six
+
These deductions were based upon a series of thirty—six injections into the‘ umbilical veins of dead pig fetuses and upon the analysis of a carefully measured calibration of the cardiac vessels of thirty—three fetuses. The injections indicated that one-half of the inferior caval stream goes to each atrium, and there are no objections to‘ such conclusions. It is Ziegenspeck’s interpretation of these results that seems to be at fault. V
injections into the‘ umbilical veins of dead pig fetuses and
 
upon the analysis of a carefully measured calibration of the
 
cardiac vessels of thirty—three fetuses. The injections indicated that one-half of the inferior caval stream goes to each
 
atrium, and there are no objections to‘ such conclusions. It
 
is Ziegenspeck’s interpretation of these results that seems to
 
be at fault. V
 
  
Pohlman shows that Ziegenspeck’s Qonclusions are incorrect, for the reason that the laws of hydrodynamics do not
+
Pohlman shows that Ziegenspeck’s Qonclusions are incorrect, for the reason that the laws of hydrodynamics do not permit vessels of the size listed to deliver the amounts of blood the arrangement calls for. Pohlman also makes the following criticism:
permit vessels of the size listed to deliver the amounts of
 
blood the arrangement calls for. Pohlman also makes the
 
following criticism:
 
  
 
In any event the results will show that measurements of this character are valueless because We must grant that:
 
In any event the results will show that measurements of this character are valueless because We must grant that:
  
1. The lumina are exactly circular.
+
# The lumina are exactly circular.
 
+
# The vessel elasticity must be equal.
2. The vessel elasticity must be equal. _
+
# The expansion of these vessels must be equal in all directions.
 
+
# The intrinsic vessel resistance must be the same.
3. The expansion of these vessels must be equal in all directions.
+
# The capillary resistance in all vessels must be equal or known.
 
+
# The quantity of blood expelled by the two sides of the heart must be the same and the pressure exacted equal. T
4. The intrinsic vessel resistance must be the same.
+
# The vessels must undergo no particular change after death and fixation.
 
 
5. The capillary resistance in all vessels must be equal or known.
 
 
 
6. The quantity of blood expelled by the two sides of the heart
 
must be the same and the pressure exacted equal. T
 
 
 
7. The vessels must undergo no particular change after death and
 
 
 
fixation.
 
 
 
Hooker’s investigations (’21), in which he shows that the
 
capillary resistance of a given capillary bed is constantly
 
changing, makes it impossible to accept proposition no. 5,
 
even though the area supplied by a given vessel might be
 
446 HOWARD B. KELLOGG
 
 
 
proportional to its carrying capacity. The marked difference
 
in the histological structure of a vein and an artery makes
 
it unsafe to assume that there is no change after death and
 
fixation, or, in case of a change, that it would have been
 
proportional to the carrying capacity of the vessel. Pohlman
 
further points out that Ziegenspeck entirely omitted the
 
following:
 
 
 
1. The azygos circulation.
 
 
 
2. The coronary circulation.
 
 
 
3. The lymphatic return to the superior Vena cava.
 
  
3. The Sabatier School
+
Hooker’s investigations (’21), in which he shows that the capillary resistance of a given capillary bed is constantly changing, makes it impossible to accept proposition no. 5, even though the area supplied by a given vessel might be proportional to its carrying capacity. The marked difference in the histological structure of a vein and an artery makes it unsafe to assume that there is no change after death and fixation, or, in case of a change, that it would have been proportional to the carrying capacity of the vessel. Pohlman further points out that Ziegenspeck entirely omitted the following:
  
Sabatier (1798) published his account of the blood flow
+
# The azygos circulation.
through the fetal heart, and it is the prevalent one to—day.
+
# The coronary circulation.
He describes the two caval streams crossing in the right
+
# The lymphatic return to the superior Vena cava.
atrium without mixing, the blood from the inferior Vena cava
 
being directed through the foramen ovale by the eustachian
 
valve to the left side of the heart and that from the superior
 
vena cava passing through the tricuspid orifice to the right
 
ventricle. T
 
  
It is evident that such an arrangement would supply the
+
===3. The Sabatier School===
head and upper extremities with blood richer in oxygen than
 
that received by the rest of the body. The more rapid development of the head, upper extremities, and liver has been
 
explained on the basis of a better blood supply to these parts.
 
  
Kilian (1826) believed that mixing of the caval streams
+
Sabatier (1798) published his account of the blood flow through the fetal heart, and it is the prevalent one to—day. He describes the two caval streams crossing in the right atrium without mixing, the blood from the inferior Vena cava being directed through the foramen ovale by the eustachian valve to the left side of the heart and that from the superior vena cava passing through the tricuspid orifice to the right ventricle. T
occurs to some extent,_but he described an aorta cerebralis,
 
which carried the best blood to the brain, and an aorta
 
abdominalis, which carried the poorer blood to the rest of
 
the body.
 
  
Reid (’35) performed three injection experiments upon
+
It is evident that such an arrangement would supply the head and upper extremities with blood richer in oxygen than that received by the rest of the body. The more rapid development of the head, upper extremities, and liver has been explained on the basis of a better blood supply to these parts.
dead human fetuses. The superior Vena cava was injected
 
with a yellow mass and the inferior Vena cava with a red
 
mass. No two of these experiments agreed. He accepted the
 
results of one injection which did not show any mixing of
 
the two fluids, and remarked that, of the remaining two, one
 
was injected in the wrong directionand the third was poorly
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 447
 
  
handled. He thus satisfied himself that the head and upper
+
Kilian (1826) believed that mixing of the caval streams occurs to some extent,_but he described an aorta cerebralis, which carried the best blood to the brain, and an aorta abdominalis, which carried the poorer blood to the rest of the body.
extremities receive fresher blood than does the rest of the
 
body. The objections to such work seem too great to require
 
much comment. First, the substances used must have had a
 
viscosity and specific gravity several times that of blood, or
 
else they would have mixed to some extent before he could
 
have opened the heart. Secondly, the heart, being dead,
 
must have been more or less rigid, whereas the living heart
 
undergoes dilatation while being filled. - He agrees that undoubtedly some organs do not require an especially rich blood
 
supply for rapid development, but that, since the brain in
 
the adult is very sensitive to minute changes in its oxygen
 
  
supply, so must it be in its growth.
+
Reid (’35) performed three injection experiments upon dead human fetuses. The superior Vena cava was injected with a yellow mass and the inferior Vena cava with a red mass. No two of these experiments agreed. He accepted the results of one injection which did not show any mixing of the two fluids, and remarked that, of the remaining two, one was injected in the wrong directionand the third was poorly handled. He thus satisfied himself that the head and upper extremities receive fresher blood than does the rest of the body. The objections to such work seem too great to require much comment. First, the substances used must have had a viscosity and specific gravity several times that of blood, or else they would have mixed to some extent before he could have opened the heart. Secondly, the heart, being dead, must have been more or less rigid, whereas the living heart undergoes dilatation while being filled. - He agrees that undoubtedly some organs do not require an especially rich blood supply for rapid development, but that, since the brain in the adult is very sensitive to minute changes in its oxygen supply, so must it be in its growth. He further states:
He further states:
 
  
And lastly when we consider the entrance of the two cavae themselves, the superior passing downwards and forwards, the inferior
+
And lastly when we consider the entrance of the two cavae themselves, the superior passing downwards and forwards, the inferior upwards and backwards, and to add to this the thick upper margin of the foramen ovale, we further perceive that the blood, passing down the cava superior must fall directly into the right auricle, to the left side of the Eustachian valve, and thus fill the right ventricle.
upwards and backwards, and to add to this the thick upper margin
 
of the foramen ovale, we further perceive that the blood, passing
 
down the cava superior must fall directly into the right auricle, to
 
the left side of the Eustachian valve, and thus fill the right ventricle.
 
  
To fulfill these conditions it is necessary to suppose that
+
To fulfill these conditions it is necessary to suppose that the fetus is kept in an upright position, or else the blood could not fall from the superior vena cava above to the right ventricle below. Pohlman ( ’07, p. 409), in his review of the Sabatier conception of the fetal circulation, raises these objections: .
the fetus is kept in an upright position, or else the blood could
 
not fall from the superior vena cava above to the right
 
ventricle below. Pohlman ( ’07, p. 409), in his review of the
 
Sabatier conception of the fetal circulation, raises these
 
objections: .
 
  
A critical examination of the theory, which by the way is the prevalent one at this time, shows it to be physically impossible, morphologically inaccurate, and developmentally unnecessary. Physically
+
A critical examination of the theory, which by the way is the prevalent one at this time, shows it to be physically impossible, morphologically inaccurate, and developmentally unnecessary. Physically impossible, because it would entail a distinct crossing of two currents under equal pressure in a distending chamber. Morphologically inaccurate, as Born has pointed out, in that no such. arrangement is found in the sauropsidian embryo, or even more strikingly in the human embryo, where the leg buds, once they appear, develop more rapidly than the arm buds when on the Sabatier principle the reverse should be the case. Developmentally unnecessary in that a number of organs grow rapidly from anlage to relatively large size without being vascularized (kidney, testes).  
impossible, because it would entail a distinct crossing of two currents
 
under equal pressure in a distending chamber. Morphologically inaccurate, as Born has pointed out, in that no such. arrangement is
 
found in the sauropsidian embryo, or even more strikingly in the
 
human embryo, where the leg buds, once they appear, develop more
 
rapidly than the arm buds when on the Sabatier principle the reverse should be the case. Developmentally unnecessary in that a
 
number of organs grow rapidly from anlage to relatively large size
 
without being vascularized (kidney, testes).
 
448 HOWARD B. KELLOGG
 
  
4. The Harvey-Pohlmcm School
+
===4. The Harvey-Pohlmcm School===
  
The rather obscure theory of the fetal circulation given by
+
The rather obscure theory of the fetal circulation given by Harvey (1628) seems, even to-day, to be correct in the main. Harvey formulated this conception after his epochal discovery of the adult pulmonary circulation andia careful study of the anatomy of the fetal heart. As Pohlman (’O9 b, p. 79) pointed out, the terminology used by Harvey has led to various interpretations. Pohlman’s careful translation of Harvey’s original description shows that Harvey believed the two caval streams to mix in the right atrium before passing to the ventricles.
Harvey (1628) seems, even to-day, to be correct in the main.
 
Harvey formulated this conception after his epochal discovery of the adult pulmonary circulation andia careful study
 
of the anatomy of the fetal heart. As Pohlman (’O9 b, p. 79)
 
pointed out, the terminology used by Harvey has led to various interpretations. Pohlman’s careful translation of Harvey’s original description shows that Harvey believed the
 
two caval streams to mix in the right atrium before passing
 
to the ventricles.
 
  
For a time Mery (1645-1722) succeeded in overshadowing
+
For a time Mery (1645-1722) succeeded in overshadowing Harvey’s work with his idea that the fetal blood flows from the left to the right atrium by means of the foramen ovale. However, Senac (1773), on repeating Mery’s injection experiments, proved them to be in error.
Harvey’s work with his idea that the fetal blood flows from
 
the left to the right atrium by means of the foramen ovale.
 
However, Senac (1773), on repeating Mery’s injection experiments, proved them to be in error.
 
  
Pohlman. (’O9 b), utilizing pig fetuses, did the first work
+
Pohlman. (’O9 b), utilizing pig fetuses, did the first work on living animals. He first determined the capacities of the two ventricles and found them to be equal. This was done by slipping a ligature around the atrioventricular sulcus and drawing it tight at the end of the atrial diastole. The blood in each ventricle was then measured. Next, he demonstrated that the pressures in both ventricles were equal by introducing identical pipettes into the two ventricles at the same time. The blood mounted equally in both pipettes. He concluded that, since there was no oscillation of the blood at the time of diastole, there could be no suction or aspiration effect due to the expanding heart. The latter had been assumed to be true for some time, but had never been proved. ,
on living animals. He first determined the capacities of the
 
two ventricles and found them to be equal. This was done
 
by slipping a ligature around the atrioventricular sulcus and
 
drawing it tight at the end of the atrial diastole. The blood
 
in each ventricle was then measured. Next, he demonstrated
 
that the pressures in both ventricles were equal by introducing identical pipettes into the two ventricles at the same
 
time. The blood mounted equally in both pipettes. He concluded that, since there was no oscillation of the blood at the
 
time of diastole, there could be no suction or aspiration effect
 
due to the expanding heart. The latter had been assumed to
 
be true for some time, but had never been proved. ,
 
  
Pohlman then made a series of injection experiments, the
+
Pohlman then made a series of injection experiments, the technique of which will be found on page 451. He injected a suspension of cornstarch into the chosen vessel and withdrew equal amounts of blood from each ventricle at the same time. Seventeen injections were forced into the umbilical veins of pig fetuses. The blood samples drawn from the ventricles were arranged in pairs for the purpose -of comparison. In five pairs neither tube contained any starch.  
technique of which will be found on page 451. He injected
 
a suspension of cornstarch into the chosen vessel and withdrew equal amounts of blood from each ventricle at the same
 
time. Seventeen injections were forced into the umbilical
 
veins of pig fetuses. The blood samples drawn from the
 
ventricles were arranged in pairs for the purpose -of comparison. In five pairs neither tube contained any starch.
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 449
 
  
Since he opened the thorax after the injections were made,
 
it is probable that in these cases the rapid fetal heart beat
 
had already passed the starch through before it could be
 
recovered. Twelve pairs showed an equal volume of starch
 
in the blood from each ventricle, and this was confirmed by
 
rough microscopic examination.
 
  
Pohlman next succeeded in making seven injectionsinto
+
Since he opened the thorax after the injections were made, it is probable that in these cases the rapid fetal heart beat had already passed the starch through before it could be recovered. Twelve pairs showed an equal volume of starch in the blood from each ventricle, and this was confirmed by rough microscopic examination.
the superior vena cava, although it was difficult to avoid
 
serious hemorrhage. From these tests he obtained four pairs
 
of tubes with equal amounts of starch inweach tube. Two
 
pairs had a difference of over 50 per cent, «but there is no.
 
record as to whether the results were consistent. One pair
 
contained no starch. He further made simultaneous injections of colored starch into the superior vena cava and an
 
uncolored starch into the inferior vena cava. After six such
 
injections, the blood recovered from each ventricle was first
 
diluted in acetic acid to destroy the erythrocytes, and then
 
compared. Both colored and uncolored granules Occurred
 
in each sample. Quantitative counts could not be made for
 
the iodine-potassium iodide used to stain the colored granules diffused too rapidly into the uncolored ones.
 
  
From these results Pohlman concluded that the caval
+
Pohlman next succeeded in making seven injectionsinto the superior vena cava, although it was difficult to avoid serious hemorrhage. From these tests he obtained four pairs of tubes with equal amounts of starch inweach tube. Two pairs had a difference of over 50 per cent, «but there is no. record as to whether the results were consistent. One pair contained no starch. He further made simultaneous injections of colored starch into the superior vena cava and an uncolored starch into the inferior vena cava. After six such injections, the blood recovered from each ventricle was first diluted in acetic acid to destroy the erythrocytes, and then compared. Both colored and uncolored granules Occurred in each sample. Quantitative counts could not be made for the iodine-potassium iodide used to stain the colored granules diffused too rapidly into the uncolored ones.
streams do mix in the right atrium and that the foramen
 
ovale does form a communication between the right and left
 
atria, instead of being placed so as to split the blood from
 
the inferior vena cava into two parts. He further declares
 
that the blood to the head and upper extremities can be of
 
no better quality than that to the rest of the body, and hence
 
the more rapid development of the upper body does not result
 
from a richer blood supply.
 
  
5. The present status of the problem
+
From these results Pohlman concluded that the caval streams do mix in the right atrium and that the foramen ovale does form a communication between the right and left atria, instead of being placed so as to split the blood from the inferior vena cava into two parts. He further declares that the blood to the head and upper extremities can be of no better quality than that to the rest of the body, and hence the more rapid development of the upper body does not result from a richer blood supply.
  
Inspection of many standard text—books of anatomy,
+
===5. The present status of the problem===
embryology, and Obstetrics, since the time of Pohlman’s
 
publication, shows a division of opinion between the Sabatier
 
and Harvey—Pohlman theories. The former is favored by a
 
large majority, several texts being non-committal in judg450 HOWARD B. KELLOGG
 
  
ment, and a few advocating the Harvey—Pohlman view. The
+
Inspection of many standard text—books of anatomy, embryology, and Obstetrics, since the time of Pohlman’s publication, shows a division of opinion between the Sabatier and Harvey—Pohlman theories. The former is favored by a large majority, several texts being non-committal in judg450 HOWARD B. KELLOGG
Ziegenspeck-Wolff conception, based chiefly upon Ziegenspeck’s interpretation of his injections of dead pig fetuses and
 
the calibration of the vessels of the heart, which since have
 
been shown to be unreliable, is no longer considered seriously.
 
  
Regarding the two rival theories, it appears that the only
+
ment, and a few advocating the Harvey—Pohlman view. The Ziegenspeck-Wolff conception, based chiefly upon Ziegenspeck’s interpretation of his injections of dead pig fetuses and the calibration of the vessels of the heart, which since have been shown to be unreliable, is no longer considered seriously.
experimental evidence in support of the Sabatier scheme is
 
that of Reid, yet his work is practically valueless, because, of
 
the three injections made upon dead human fetuses, no two
 
agreed. The anatomical evidence supporting this view is
 
based upon the position of the eustachian valve. This, however, does not seem to be adequate, for although in a fixed,
 
motionless heart the valve might be capable of directing all
 
of the inferior caval blood through the foramen ovale, nevertheless, it must lose most of its positional advantage in the
 
distending heart. The supposed morphological necessity of
 
such a condition may be disregarded, since Born (’89) and
 
Pohlman (’07,"p. 409) have argued convincingly from analogy
 
that the more rapid development of the head and upper extremities does not necessarily depend upon a superior blood
 
supply. On the contrary, it can be urged that the anatomical
 
relations may be interpreted equally as evidence in support
 
of either the Sabatier or Harvey-Pohlman theory.
 
  
The work of Pohlman, although highly suggestive and
+
Regarding the two rival theories, it appears that the only experimental evidence in support of the Sabatier scheme is that of Reid, yet his work is practically valueless, because, of the three injections made upon dead human fetuses, no two agreed. The anatomical evidence supporting this view is based upon the position of the eustachian valve. This, however, does not seem to be adequate, for although in a fixed, motionless heart the valve might be capable of directing all of the inferior caval blood through the foramen ovale, nevertheless, it must lose most of its positional advantage in the distending heart. The supposed morphological necessity of such a condition may be disregarded, since Born (’89) and Pohlman (’07,"p. 409) have argued convincingly from analogy that the more rapid development of the head and upper extremities does not necessarily depend upon a superior blood supply. On the contrary, it can be urged that the anatomical relations may be interpreted equally as evidence in support of either the Sabatier or Harvey-Pohlman theory.
unique in its employment of experimentation on living animals, has lacked conviction, because his conclusions were
 
based upon relatively few experiments. There is also a
 
doubt as to their exactness, due to the theoretical disturbances
 
of the circulation brought about by injecting a foreign substance into the heart and then piercing the heart to remove
 
it. For these reasons and with the hope of gaining more
 
precise information as to the degree of blood admixture in
 
the heart, a program of experimentation was outlined. In
 
this it was first decided to repeat, expand, and, if possible,
 
improve on Pohlman’s type of experiments. It is with these
 
results that the present paper is concerned. In a subsequent
 
contribution more refined quantitative determinations, using
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 451
 
  
the methods of gas analysis which eliminate some of the more
+
The work of Pohlman, although highly suggestive and unique in its employment of experimentation on living animals, has lacked conviction, because his conclusions were based upon relatively few experiments. There is also a doubt as to their exactness, due to the theoretical disturbances of the circulation brought about by injecting a foreign substance into the heart and then piercing the heart to remove it. For these reasons and with the hope of gaining more precise information as to the degree of blood admixture in the heart, a program of experimentation was outlined. In this it was first decided to repeat, expand, and, if possible, improve on Pohlman’s type of experiments. It is with these results that the present paper is concerned. In a subsequent contribution more refined quantitative determinations, using the methods of gas analysis which eliminate some of the more serious theoretical objections, will be reported.
serious theoretical objections, will be reported.
 
  
I wish to express my great appreciation to Dr. L. B. Arey
+
I wish to express my great appreciation to Dr. L. B. Arey for suggesting this problem and also for his constant assistance during the work. The generous cooperation of Swift & Company, Chicago, expedited the work.
for suggesting this problem and also for his constant assistance during the work. The generous cooperation of
 
Swift & Company, Chicago, expedited the work.
 
  
EXPERIMENTAL
+
==Experimental==
  
 
Starch and ink injections
 
Starch and ink injections
  
The method of starch injections, as used by Pohlman, with
+
The method of starch injections, as used by Pohlman, with some changes in technique was employed and a series of over 200 observations has been obtained.
some changes in technique was employed and a series of over
 
200 observations has been obtained.
 
  
Materials and methods. This type of experimentation is
+
Materials and methods. This type of experimentation is not dependent upon a normal placental exchange, and therefore permits the choice of pig fetuses as material. The large size and the availability of these fetuses is a distinct advantage in such work. In addition, one pregnant dog was secured and used while the placental circulation of both mother and fetuses was intact.
not dependent upon a normal placental exchange, and therefore permits the choice of pig fetuses as material. The large
 
size and the availability of these fetuses is a distinct advantage in such work. In addition, one pregnant dog was
 
secured and used while the placental circulation of both
 
mother and fetuses was intact.
 
  
The pig experiments were done on the killing floor of Swift
+
The pig experiments were done on the killing floor of Swift & Company, Chicago. Operative conditions were not the best, but the abundance of material compensated for any inconveniences. Fifteen to thirty minutes after killing, the sows were opened, the uterus cut at the cervix and handed to the experimenter. This lapse of time and the drainage of blood from the sow had a material effect upon the procural of suitable living material. About one uterus out of four of those large enough to use contained fetuses that maintained a sufficiently vigorous heart beat; the only blood samples retained were those taken from pigs whose hearts continued to beat at least ten times after the blood was withdrawn. When received, the uterus was opened at once along its least vascular border and the fetus removed with a minimum disturbance to the placenta and fetal circulation. It is possible to cut away the ventral thoracic wall and open the pericardium with but slight hemorrhage. In this manner the  
& Company, Chicago. Operative conditions were not the
+
heart is made freely accessible for rapid observation and blood sampling before beginning the experimental procedure. It is important to eliminate the possibility of error through delay or by mechanical violence in exposing the field of operation.
best, but the abundance of material compensated for any
 
inconveniences. Fifteen to thirty minutes after killing, the
 
sows were opened, the uterus cut at the cervix and handed
 
to the experimenter. This lapse of time and the drainage of
 
blood from the sow had a material effect upon the procural
 
of suitable living material. About one uterus out of four of
 
those large enough to use contained fetuses that maintained a
 
sufficiently vigorous heart beat; the only blood samples retained were those taken from pigs whose hearts continued
 
to beat at least ten times after the blood was withdrawn.
 
When received, the uterus was opened at once along its least
 
vascular border and the fetus removed with a minimum disturbance to the placenta and fetal circulation. It is possible
 
to cut away the ventral thoracic wall and open the pericardium with but slight hemorrhage. In this manner the
 
452 HOWARD B. KELLOGG
 
  
heart is made freely accessible for rapid observation and
+
The type of experimentation employed was the injecting of suspensions into the superior and inferior venae cavae and then either observing the visible effect on the two halves of the heart or making controlled computations of the contained blood-suspension mixture. The first result is qualitative, but possesses the merit of furnishing ocular proof without the introduction of additional manipulative factors; the second is quantitative, and, properly controlled, affords a basis for definite mathematical comparisons. .
  
blood sampling before beginning the experimental procedure.
+
The technique of the direct-observation experiments was simple. Suspensions of India ink or of 10 per cent cornstarch in physiological salt solution were introduced into the selected vessel by means of a hypodermic syringe, whereupon the resultant color change in the heart was noted.
It is important to eliminate the possibility of error through
 
delay or by mechanical violence in exposing the field of
 
operation.
 
  
The type of experimentation employed was the injecting of
+
The objective of the quantitative tests was to obtain from many experiments a more accurate estimate of the extent of admixture of the two caval streams within the right atrium. This was to be done by introducing starch into a vein and then making counts of ‘the granules obtained from samples of blood withdrawn simultaneously from the two ventricles. Further checks were to be secured by comparison of the amounts of starch which settled out differentially from samples of blood allowed to stand in narrow tubes.
suspensions into the superior and inferior venae cavae and
 
then either observing the visible effect on the two halves of
 
the heart or making controlled computations of the contained
 
blood-suspension mixture. The first result is qualitative, but
 
possesses the merit of furnishing ocular proof without the
 
introduction of additional manipulative factors; the second
 
is quantitative, and, properly controlled, affords a basis for
 
definite mathematical comparisons. .
 
  
The technique of the direct-observation experiments was
+
A 10 per cent starch suspension was introduced into the selected vessel by means of a hypodermic syringe and three to ten seconds later equal quantities of blood were withdrawn from the two ventricles with identical pipettes. It was necessary to use caution in the rate and amount of the injection to avoid excessive pressure within the vessel. The pipettes used were small pieces of glass tubing, held together by rubber bands, to which no. 20 needles were attached. The opposite ends of the pipettes were connected to a Y-tube by means of rubber tubing. By sucking gently on the stem of the Y, a common negative pressure was imparted to each needle, and equal volumes of blood were usuallyobtained. Samples with appreciable differences in volume were rejected. The two samples thus obtained were then drained into paired vials, each containing ‘two drops of potassium oxalate. This amount of oxalate prevented clotting and was not sufficient to introduce any significant error in the results.
simple. Suspensions of India ink or of 10 per cent cornstarch in physiological salt solution were introduced into the
 
selected vessel by means of a hypodermic syringe, whereupon
 
the resultant color change in the heart was noted.
 
  
The objective of the quantitative tests was to obtain from
+
When making a starch count, the blood was diluted one hundred times in a solution which contained a small amount of potassium iodide and iodine; the starch granules stained well with the iodine. Counts were made, using the chamber regularly employed in clinical blood computations. It was found that the specific gravity of starch granules is so high that they do not always spread evenly, but may tend to settle out on the slide near the point where the drop was emitted from the mixing pipette. To equalize this tendency, four counts were made from each sample, and the average value then used.
many experiments a more accurate estimate of the extent
 
of admixture of the two caval streams within the right atrium.
 
This was to be done by introducing starch into a vein and
 
then making counts of ‘the granules obtained from samples of
 
blood withdrawn simultaneously from the two ventricles.
 
Further checks were to be secured by comparison of the
 
amounts of starch which settled out differentially from
 
samples of blood allowed to stand in narrow tubes.  
 
  
A 10 per cent starch suspension was introduced into the
+
When blood containing starch is allowed to settle undisturbed, the starch granules, because of their greater specific gravity, occupy a bottom layer; next come the cellular ele -ments, whereas the highest stratum is of clear serum. This
selected vessel by means of a hypodermic syringe and three
 
to ten seconds later equal quantities of blood were withdrawn
 
from the two ventricles with identical pipettes. It was necessary to use caution in the rate and amount of the injection
 
to avoid excessive pressure within the vessel. The pipettes
 
used were small pieces of glass tubing, held together by
 
rubber bands, to which no. 20 needles were attached. The
 
opposite ends of the pipettes were connected to a Y-tube
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 453»
 
  
by means of rubber tubing. By sucking gently on the stem
+
differential sorting is preferable to separation by centrifuging. The volume of blood usually obtained in a single sample is 1 cc.,. but this amount is not sufficient to allow comparisons of the settled starch in ordinary centrifuge tubes. To overcome this difficulty, each tube received an equal quantity from eight to twelve corresponding pairs of samples. Composite columns of blood, 5 to 6 cm. in height, were thus obtained.
of the Y, a common negative pressure was imparted to each
 
needle, and equal volumes of blood were usuallyobtained.
 
Samples with appreciable differences in volume were rejected.
 
The two samples thus obtained were then drained into paired
 
vials, each containing ‘two drops of potassium oxalate. This
 
amount of oxalate prevented clotting and was not sufficient to
 
introduce any significant error in the results.
 
  
When making a starch count, the blood was diluted one
+
On the contrary, individual tubes were also prepared from glass tubing with a3-mm. bore. These tubes gave a column of blood from a single sample ‘sufficiently high for the purpose of comparison. A large drop of mercury placed in the bottom of each tube produced a surface upon which the starch settled; this eliminated errors due to unequal curvatures at the sealed ends.
hundred times in a solution which contained a small amount
 
of potassium iodide and iodine; the starch granules stained
 
well with the iodine. Counts were made, using the chamber
 
regularly employed in clinical blood computations. It was
 
found that the specific gravity of starch granules is so high
 
that they do not always spread evenly, but may tend to settle
 
out on the slide near the point where the drop was emitted
 
from the mixing pipette. To equalize this tendency, four
 
counts were made from each sample, and the average value
 
then used.
 
  
When blood containing starch is allowed to settle undisturbed, the starch granules, because of their greater specific
+
Observations. 1. Direct inspection of heart. Careful observation of the fetal pig heart showed that almost immediately after an injection of the starch suspension into the umbilical or external jugular vein both ventricles blanched. The apices of the two ventricles, being thinner than the rest, showed this decoloration very markedly. Similarly, when India ink was introduced into the veins, it was obvious that both ventricles became equally black at once. These injections were repeated on about 125 fetuses of various ages, and in every instance the discoloration occurred equally in both ventricles at the same moment. These observations, while not primarily of a quantitative value, constitute definite evidence proving beyond a doubt that the two caval streams do mingle in the right atrium, whereupon both ventricles receive mixed arteriovenous blood. They are especially important, because they involve no subsequent disturbance of the heart.
gravity, occupy a bottom layer; next come the cellular ele
 
-ments, whereas the highest stratum is of clear serum. This
 
  
differential sorting is preferable to separation by centrifuging. The volume of blood usually obtained in a single sample
+
After the starch injections are made, the heart usually continues to beat at its regular rate, but frequently the heart is accelerated. This augmentation is probably due to the warmth of the starch solution or to a slight increase in pressure. Inthe case of the ink, which is toxic, the heart usually stopped within three to ten pulsations after the fluid reached the ventricles.
is 1 cc.,. but this amount is not sufficient to allow comparisons
 
of the settled starch in ordinary centrifuge tubes. To overcome this difficulty, each tube received an equal quantity from
 
eight to twelve corresponding pairs of samples. Composite
 
columns of blood, 5 to 6 cm. in height, were thus obtained.
 
  
On the contrary, individual tubes were also prepared from
+
Similar observations were made on five living dog fetuses, delivered under ether anaesthesia. The maternal and fetal circulations continued normally. The results from injections into the umbilical vein were identical with those obtained with pigs. The importance of such direct observations cannot be overemphasized.
  
' glasstubing with a3-mm. bore. These tubes gave a column
+
2. Quantitative determinations. A. Results on pigs. a. Quantitative counts. Starch granules were counted in selected unit areas of the ruled chamber and the totals from ten fetuses summated. Such grand counts from pig fetuses that had received injections into their umbilical veins gave a ratio of 253 in blood withdrawn from the right ventricle to 293 in that from the left. On the basis of these results alone, the inference is that the left ventricle received 16 per cent more blood from the inferior vena cava than did the right (but see p. 458).
  
of blood from a single sample ‘sufficiently high for the purpose
+
12. Volume comparison. Three sets of composite tubes, each containing equal amounts from eight, nine, and twelve paired samples,’ respectively, were prepared from blood taken after the fetuses had received starch injections into the umbilical veins. From these a column of starch about 53 inch high Settled out. There was no appreciable difference in the amount of starch representing the right and left ventricles.
of comparison. A large drop of mercury placed in the bottom
 
of each tube produced a surface upon which the starch settled;
 
this eliminated errors due to unequal curvatures at the sealed
 
ends.
 
454 ' HOWARD B. KELLOGG
 
  
Observations. 1. Direct inspection of heart. Careful observation of the fetal pig heart showed that almost immediately after an injection of the starch suspension into the
+
Thirty—three paired sets from umbilical—vein injections and thirty sets from external jugular-vein injections were next prepared. Each blood sample was placed in an individual narrow tube (compare p. 456). These occasionally showed a small difference in the amount of starch representing the right and left ventricles, but such variation was not consistently in one direction and the series as a whole essentially balanced. (Figures 1 to 3 illustrate well the type of result obtained from such injections.) The small bore of the indi~ vidual tubes made it difiicult always to introduce the complete sample into the tube. For this reason, the starch columns must in each instance be compared with the height of the corresponding column of blood. It is evident that in most paired samples the quantity of starch in each tube was proportionally the same.
umbilical or external jugular vein both ventricles blanched.
 
The apices of the two ventricles, being thinner than the rest,
 
showed this decoloration very markedly. Similarly, when
 
India ink was introduced into the veins, it was obvious that
 
both ventricles became equally black at once. These injections were repeated on about 125 fetuses of various ages, and
 
in every instance the discoloration occurred equally in both
 
ventricles at the same moment. These observations, while
 
not primarily of a quantitative value, constitute definite evidence proving beyond a doubt that the two caval streams do
 
mingle in the right atrium, whereupon both ventricles receive
 
mixed arteriovenous blood. They are especially important,
 
because they involve no subsequent disturbance of the heart.
 
  
After the starch injections are made, the heart usually
+
B. Results on dogs. The dog fetuses were too small (although well toward the end of gestation) to attempt ex_ternal jugular-vein injections. Hence, the five fetuses were injected through the umbilical veins only and the samples placed in individual sets of small tubes. There was more variation in the corresponding tubes of this series (fig. 3), the ratio between the right and left ventricle samples ranging from 10:11.7 to 5228.5, respectively; the average being 25.3): 33, respectively. Nevertheless, this difference is probably capable of explanation on the basis of technical procedure rather than representing a natural relation (p. 458).  
continues to beat at its regular rate, but frequently the heart
 
is accelerated. This augmentation is probably due to the
 
warmth of the starch solution or to a slight increase in pressure. Inthe case of the ink, which is toxic, the heart usually
 
stopped within three to ten pulsations after the fluid reached
 
the ventricles.
 
  
Similar observations were made on five living dog fetuses,
 
delivered under ether anaesthesia. The maternal and fetal
 
circulations continued normally. The results from injections
 
into the umbilical vein were identical with those obtained
 
with pigs. The importance of such direct observations cannot be overemphasized.
 
  
2. Quantitative determinations. A. Results on pigs. a.
+
Fig. 1 A series of ten pairs of tubes containing blood taken simultaneously from the right and left ventricles of pig fetuses after the injection of a starch suspension into the umbilical vein.
Quantitative counts. Starch granules were counted in selected
 
unit areas of the ruled chamber and the totals from ten
 
fetuses summated. Such grand counts from pig fetuses that
 
had received injections into their umbilical veins gave a ratio
 
of 253 in blood withdrawn from the right ventricle to 293 in
 
that from the left. On the basis of these results alone, the
 
inference is that the left ventricle received 16 per cent more
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 455
 
  
blood from the inferior vena cava than did the right (but
 
see p. 458). _
 
  
12. Volume comparison. Three sets of composite tubes, each
+
Fig. 2 A series of ten pairs of tube containing blood taken simultaneously from the right and left ventricles of pig fetuses after 3. starch suspension was injected into the external jugular vein.  
containing equal amounts from eight, nine, and twelve paired
 
samples,’ respectively, were prepared from blood taken after
 
the fetuses had received starch injections into the umbilical
 
veins. From these a column of starch about 53 inch high
 
Settled out. There was no appreciable difference in the
 
amount of starch representing the right and left ventricles.
 
  
Thirty—three paired sets from umbilical—vein injections and
 
thirty sets from external jugular-vein injections were next
 
prepared. Each blood sample was placed in an individual
 
narrow tube (compare p. 456). These occasionally showed a
 
small difference in the amount of starch representing the
 
right and left ventricles, but such variation was not consistently in one direction and the series as a whole essentially
 
balanced. (Figures 1 to 3 illustrate well the type of result
 
obtained from such injections.) The small bore of the indi~
 
vidual tubes made it difiicult always to introduce the complete
 
sample into the tube. For this reason, the starch columns
 
must in each instance be compared with the height of the
 
corresponding column of blood. It is evident that in most
 
paired samples the quantity of starch in each tube was proportionally the same.
 
  
B. Results on dogs. The dog fetuses were too small
 
(although well toward the end of gestation) to attempt ex_ternal jugular-vein injections. Hence, the five fetuses were
 
injected through the umbilical veins only and the samples
 
placed in individual sets of small tubes. There was more
 
variation in the corresponding tubes of this series (fig. 3),
 
the ratio between the right and left ventricle samples ranging
 
from 10:11.7 to 5228.5, respectively; the average being
 
25.3): 33, respectively. Nevertheless, this difference is prob
 
ably capable of explanation on the basis of technical procedure rather than representing a natural relation (p. 458).
 
456 HOWARD B. KELLOGG
 
  
+
Fig. 3 A series of five pairs of tubes containing blood taken simultaneously from the right and left ventricles of dog fetuses after the injection of a starch suspension into the umbilical vein.
  
Fig. 1 A series of ten pairs of tubes containing blood taken simultaneously
+
EXPLANATION or FIGURES 1, 2, AND 3
from the right and left ventricles of pig fetuses after the injection of a starch
 
suspension into the umbilical vein.
 
  
+
As stated in the text, it was impossible always to fill the 3-mm. tubes to the same level. Hence, for purposes of ready comparison, all columns of blood in the accompanying illustrations have been reduced to the same height, and the starch columns have been similarly corrected and reproduced in their exact ratios. . '
  
Fig. 2 A series of ten pairs of tube containing blood taken simultaneously
+
The letter L and R at the bottom of the tubes indicate that the blood was taken from the left or right ventricle. The solid block at the bottom of the tube represents the mercury put in to give an even surface for the starch to settle upon. The short white columns above the block repreent the sedimented starch, and the stippled strata correspond to the supernatant blood. 458 HOWARD 13. KELLOGG
from the right and left ventricles of pig fetuses after 3. starch suspension was
 
injected into the external jugular vein.
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 457
 
  
+
==Discussion==
  
LR LR LR LR LR
+
The ocular observations of the starch and ink injections show clearly that the two caval streams do mix in the right atrium, while the starch counts and the sedimentation experiments are a quantitative proof that the two sides of the heart receive blood of approximately the same character.
  
Fig. 3 A series of five pairs of tubes containing blood taken simultaneously
+
The results, obtained in the pig series of over 100 injections and 125 direct observations of the heart, show some discrepancies, but they are not great and could, no doubt, be eliminated if a better control of operative conditions were possible (compare p. 451).
from the right and left ventricles of dog fetuses after the injection of a starch
 
suspension into the umbilical vein.
 
  
EXPLANATION or FIGURES 1, 2, AND 3
+
The heart beat of the fetal dogs was so rapid, due to their normal uninterrupted oxygen supply, that it seemed advisable to make the injection much faster than usual to prevent the starch from being pumped through the heart before the samples could be withdrawn. In doing this there is little doubt that the pressure in the inferior vena cava was raised considerably above normal. Since the foramen ovale is in a more direct line with the inferior caval blood stream than is the tricuspid orifice, an increased pressure in the inferior cava would. tend to drive more than the usual amount of its blood through the foramen ovale. While these results showed the greatest variation of any in the present series, they nevertheless afford very important evidence in support of the Harvey-Pohlman theory, since they are the first obtained on animals in which both the maternal and fetal sides of the placental circulation were intact and the other general conditions approached normality.
  
As stated in the text, it was impossible always to fill the 3-mm. tubes to the
 
same level. Hence, for purposes of ready comparison, all columns of blood in
 
the accompanying illustrations have been reduced to the same height, and the
 
starch columns have been similarly corrected and reproduced in their exact
 
ratios. . '
 
  
The letter L and R at the bottom of the tubes indicate that the blood was
+
The small percentage in favor of the left side of the heart receiving more pure blood, as indicated by the results obtained from the starch counts, may well be within the error introduced from the failure of the starch granules to spread evenly on the counting chamber. These results were all from the earlier injections, and again it is likely that the then undeveloped technique in controlling. the rate- of injection would account for more of the inferior caval stream going through the foramen ovale.
taken from the left or right ventricle. The solid block at the bottom of the
 
tube represents the mercury put in to give an even surface for the starch to
 
settle upon. The short white columns above the block repreent the sedimented
 
starch, and the stippled strata correspond to the supernatant blood.
 
458 HOWARD 13. KELLOGG
 
  
DISCUSSION
 
  
The ocular observations of the starch and ink injections
+
Pohlman had difficulty in obtaining starch in all of the samples; seven out of twenty-nine sets contained no starch at all. This undoubtedly was due to the fact that he delayed too long his Withdrawal of the samples by opening the thorax after making the injections. By reversing these procedures in the present investigation, but three sets showing no starch were obtained in over a hundred samples. Pohlman also found great difliculty in opening the thorax sufficiently high to expose the superior vena cava without severe hemorrhage ensuing; additional hemorrhage occurred as Well when the needle was Withdrawn after the injection had been made into the superior vena cava. By using the external jugular vein as an avenue to the superior cava, it was not necessary to open the thorax so high, and there was also no hemorrhage after the needle was "Withdrawn from, the small vein. The small size of the external jugular vein made only the larger pigs of value for this injection; many experiments Were rejected before the recorded numbers of successful injections were obtained.
show clearly that the two caval streams do mix in the right
 
atrium, while the starch counts and the sedimentation experiments are a quantitative proof that the two sides of the heart
 
receive blood of approximately the same character.
 
  
The results, obtained in the pig series of over 100 injections and 125 direct observations of the heart, show some
+
The direct observations of the heart While starch and ink injections were made is so simple and reliable, for it eliminates the possibilities of induced error resulting from the trauma of pipettes, that it cannot be overemphasized as a critical method of attack. .
discrepancies, but they are not great and could, no doubt, be
 
eliminated if a better control of operative conditions were
 
possible (compare p. 451).
 
  
The heart beat of the fetal dogs was so rapid, due to their
+
It is stated by some authorities that, as the fetus nears the end of the gestation period, the foramen ovale and ductus arteriosus become proportionally smaller and smaller with the concomitant increase in the blood flowing through the lungs. If this were true, the fetal circulation would approach the adult type before birth. To gain information on this point, complete records were kept of the lengths of all pig fetuses. The pig fetuses varied from 6 to 14 inches in length. Pig fetuses 14 inches in length are nearly at term.
normal uninterrupted oxygen supply, that it seemed advisable to make the injection much faster than usual to prevent
 
the starch from being pumped through the heart before the
 
samples could be withdrawn. In doing this there is little
 
doubt that the pressure in the inferior vena cava was raised
 
considerably above normal. Since the foramen ovale is in
 
a more direct line with the inferior caval blood stream than
 
is the tricuspid orifice, an increased pressure in the inferior
 
cava would. tend to drive more than the usual amount of its
 
blood through the foramen ovale. While these results showed
 
the greatest variation of any in the present series, they nevertheless afford very important evidence in support of the
 
Harvey-Pohlman theory, since they are the first obtained on
 
animals in which both the maternal and fetal sides of the
 
placental circulation were intact and the other general conditions approached normality. M
 
  
The small percentage in favor of the left side of the heart
+
It was not possible to correlate any difference in the proportion of caval blood going to each ventricle with increasing size. A careful examination of a considerable number of fetal hearts seems to show that the foramen ovale maintains its relative size throughout fetal life, but that the two atrial septa (primum and secundum) do become much larger in the late stages of gestation. Yet, while the septa do more nearly overlap, they are so placed that the blood may pass freely from the right to the left atrium until such time as there is an increased pressure in the left atrium to hold them in apposition. This, however, cannot take place until the respiration at birth forces a greater amount of blood through the lungs.
receiving more pure blood, as indicated by the results obtained from the starch counts, may well be within the error
 
introduced from the failure of the starch granules to spread
 
evenly on the counting chamber. These results were all
 
from the earlier injections, and again it is likely that the
 
then undeveloped technique in controlling. the rate- of injection would account for more of the inferior caval stream
 
going through the foramen ovale.
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 459
 
  
Pohlman had difficulty in obtaining starch in all of the
+
It will be remembered that Reid furnished the only experimental support to the popular Sabatier theory, but that his results are too meager and uncritical to be of any real value (p. 446); at best, the Sabatier conception is a mere philosophical argument, based on the supposed advantages that would accrue from a differential segregation of pure and impure blood.
samples; seven out of twenty-nine sets contained no starch
 
at all. This undoubtedly was due to the fact that he delayed
 
too long his Withdrawal of the samples by opening the thorax
 
after making the injections. By reversing these procedures
 
in the present investigation, but three sets showing no starch
 
were obtained in over a hundred samples. Pohlman also
 
found great difliculty in opening the thorax sufficiently high
 
to expose the superior vena cava without severe hemorrhage
 
ensuing; additional hemorrhage occurred as Well when the
 
needle was Withdrawn after the injection had been made into
 
the superior vena cava. By using the external jugular vein
 
as an avenue to the superior cava, it was not necessary to
 
open the thorax so high, and there was also no hemorrhage
 
after the needle was "Withdrawn from, the small vein. The
 
small size of the external jugular vein made only the larger
 
pigs of value for this injection; many experiments Were rejected before the recorded numbers of successful injections
 
were obtained.
 
  
The direct observations of the heart While starch and ink
+
On the contrary, the results presented in the present investigation agree exactly with those of Pohlman and attest to the fundamental correctness of the Harvey—Pohlman view. The fact that the present results were obtained from a large series of animals and several methods of attack (i.e., ocular observation, starch counts, and sedimentation of starch on living fetuses, some of which had normal placental relations) makes them much more trustworthy than those of but one method. If there is any difference in the quality of blood furnished to the different parts of the body, the amount is quantitative and not significant.
injections were made is so simple and reliable, for it eliminates the possibilities of induced error resulting from the
 
trauma of pipettes, that it cannot be overemphasized as a
 
critical method of attack. .
 
  
It is stated by some authorities that, as the fetus nears the
+
To those who obtain mental satisfaction from fitting supposedly advantageous mechanisms to physiological ideals, the Harvey—Pol1lman theory may be disappointing. Yet it is by no "means certain that there is any necessity in "maintaining a difference in the quality of blood distributed to the various parts of the body. Circulatory efficiency in the mammalian embryo doubtless depends jointly on the relatively large quantity of swiftly moving blood and on the large factor of safety in the oxygen supply.
end of the gestation period, the foramen ovale and ductus
 
arteriosus become proportionally smaller and smaller with
 
the concomitant increase in the blood flowing through the
 
lungs. If this were true, the fetal circulation would approach
 
the adult type before birth. To gain information on this
 
point, complete records were kept of the lengths of all pig
 
fetuses. The pig fetuses varied from 6 to 14 inches in length.
 
Pig fetuses 14 inches in length are nearly at term.
 
  
It was not possible to correlate any difference in the proportion of caval blood going to each ventricle with increasing
 
size. A careful examination of a considerable number of
 
fetal hearts seems to show that the foramen ovale maintains
 
  
THE AMERICAN JOURNAL OF ANATOMY, VOL. 42, NO. 2
+
At the outset it was recognized that the injection of starch granules into the venae cavae as a method of attacking this problem has certain theoretical shortcomings. Objections to this type of experimentation apply especially to any quantitative deductions that may be made.
460 HOWARD B. KELLOGG
 
  
its relative size throughout fetal life, but that the two atrial
+
Possible errors might be expected to result from:
septa (primum and secundum) do become much larger in
 
the late stages of gestation. Yet, while the septa do more
 
nearly overlap, they are so placed that the blood may pass
 
freely from the right to the left atrium until such time as
 
there is an increased pressure in the left atrium to hold them
 
in apposition. This, however, cannot take place until the
 
respiration at birth forces a greater amount of blood through
 
the lungs.
 
  
It will be remembered that Reid furnished the only experimental support to the popular Sabatier theory, but that his
+
# The introduction of a foreign substance into the blood stream.
results are too meager and uncritical to be of any real value
+
# Blockage by the starch granules of the capillary beds beyond the heart, which would result in stasis and churning of the blood within the heart.
(p. 446); at best, the Sabatier conception is a mere philosophical argument, based on the supposed advantages that
+
# The interference with heart action by piercing it when drawing samples.
would accrue from a differential segregation of pure and
+
# Injection of starch suspensions under such great pressure that the equilibrium of the two caval streams entering the right atria would be disturbed.
impure blood.
+
# Withdrawing samples from the two ventricles under unequal negative pressures, which likewise would change the natural circulation within the heart.
  
On the contrary, the results presented in the present investigation agree exactly with those of Pohlman and attest
 
to the fundamental correctness of the Harvey—Pohlman view.
 
The fact that the present results were obtained from a large
 
series of animals and several methods of attack (i.e., ocular
 
observation, starch counts, and sedimentation of starch on
 
living fetuses, some of which had normal placental relations)
 
makes them much more trustworthy than those of but one
 
method. If there is any difference in the quality of blood
 
furnished to the different parts of the body, the amount is
 
quantitative and not significant.
 
  
To those who obtain mental satisfaction from fitting supposedly advantageous mechanisms to physiological ideals,
+
The objection to the introduction of a foreign substance into the blood stream can be minimized if the material used is not toxic and the viscosity and specific gravity are not at too great variance with that of normal blood. The starch suspensions in physiological saline are not toxic. It is true the viscosity of the solution is somewhat less than that of blood and the specific gravity of starch granules is greater than that of blood corpuscles. However, in a blood stream that is moving at a normal rate these diiferences are probably not large enough to have noticeable effect.
the Harvey—Pol1lman theory may be disappointing. Yet it
 
is by no "means certain that there is any necessity in "maintaining a difference in the quality of blood distributed to the
 
various parts of the body. Circulatory efficiency in the mammalian embryo doubtless depends jointly on the relatively
 
large quantity of swiftly moving blood and on the large
 
factor of safety in the oxygen supply.
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART 461
 
  
At the outset it was recognized that the injection of starch
+
The possibility of vascular stasis resulting from blockage of the capillary bed beyond the heart'seems to be the most serious feature of this type of experimentation. Undoubtedly, stasis in the heart would result in churning of the blood and a consequent admixture through the foramen ovale of the blood in the two sides of the heart. That this did not occur seems evident by the fact that no marked change in the heart rate nor in the amplitude of contraction and dilatation occurred. It is well recognized that a sudden blockage of blood leaving the heart will cause dilatation, especially of the atria, a slowing of the rate, and contractions of a more forceful character. Further, the results seldom showed exactly the same amount of starch in the two sides of the heart and the Variations were not constant in any one direction. Had stasis and churning occurred, one might expect the samples from the two sides of the heart to contain equal quantities of starch. On the contrary, the inconstant Variation obtained seems to indicate a slight variable error due to different degrees of mixing in the heart itself.
granules into the venae cavae as a method of attacking this
 
problem has certain theoretical shortcomings. Objections to
 
this type of experimentation apply especially to any quantitative deductions that may be made.
 
  
Possible errors might be expected to result from:
+
Interference to heart action resulting from the introduction of sharp needles for the purpose of withdrawing samples can hardly be a serious objection, since the heart continued to beat regularly and normally and the samples were secured within two or three contractions after the needles were inserted.
  
1. The introduction of a foreign substance into the blood
+
Too rapid a rate of injection of the starch suspensions might introduce considerable error. As has been pointed out in the discussion of the results obtained with dog fetuses, too rapid injection into the umbilical Vein may result in more than the normal amount of inferior vena cava blood passing through the foramen ovale to the left side of the heart.
stream.
 
  
2. Blockage by the starch granules of the capillary beds
+
In any series of injections where such technique was employed throughout there undoubtedly would be a constant predominance of starch found in the left heart. This occurred in the dog series only. It might likewise be assumed that too rapid injection into the superior vena cava would result in a greater quantity of starch going to the right heart.
beyond the heart, which would result in stasis and churning
 
of the blood within the heart.
 
  
3. The interference with heart action by piercing it when
+
In the present series of experiments none of the superior Vena-cava injections was made rapidly, and since there was no predominance in favor of the right heart, it seems certain that these injections were not too rapid.
drawing samples.
 
  
4. Injection of starch suspensions under such great pressure that the equilibrium of the two caval streams entering
+
Since in the dog series only, in which injection was purposely much faster than in the pig series, was there a predominance in the amount of starch found in one side of the heart, it follows that the rate of injection, if properly controlled, is not necessarily a source of great error.  
the right atria would be disturbed.
 
  
5. Withdrawing samples from the two ventricles under
 
unequal negative pressures, which likewise would change the
 
natural circulation within the heart.
 
  
The objection to the introduction of a foreign substance
+
Differences in the negative pressure applied to the two needles might cause the blood to be sucked by way of the foramen ovale from the side of the heart of least negative pressure to the side containing the needle of greatest negative pressure. This was overcome by the use of the Y tube connected to the two needles, as already described (p. 452). That the samples obtained simultaneously from the two sides of the heart were approximately always equal in amount is good and sufficient proof that this did not occur.
into the blood stream can be minimized if the material used
 
is not toxic and the viscosity and specific gravity are not at
 
too great variance with that of normal blood. The starch
 
suspensions in physiological saline are not toxic. It is true
 
the viscosity of the solution is somewhat less than that of
 
blood and the specific gravity of starch granules is greater
 
than that of blood corpuscles. However, in a blood stream
 
that is moving at a normal rate these diiferences are probably not large enough to have noticeable effect.
 
  
The possibility of vascular stasis resulting from blockage
+
It is evident that the above objections apply chiefly to the quantitative results and, to a much less degree, to the ocular observations of the ink and starch injections.
of the capillary bed beyond the heart'seems to be the most
 
serious feature of this type of experimentation. Undoubtedly,
 
stasis in the heart would result in churning of the blood and
 
a consequent admixture through the foramen ovale of the
 
blood in the two sides of the heart. That this did not occur
 
  
seems evident by the fact that no marked change in the heart.
+
Even though the theoretical objections to the injection method seem to have been sufficiently overcome in its practical application, fear that some might still be skeptical has led to a search for a new and more refined quantitative means of approach.
  
rate nor in the amplitude of contraction and dilatation oc462 HOWARD B. KELLOGG
+
The development of the Van Slyke micro gas analysis of blood for its oxygen and carbon-dioxide content has ideally satisfied this demand. This method makes it possible to determine with chemical exactness the amount of oxygen and carbon dioxide present in the blood of the various vessels of the fetus.
  
curred. It is well recognized that a sudden blockage of blood
+
The results and technique of gas analysis will appear in a separate publication. It may be stated here that the results of gas analysis have shown beyond all doubt that the starchinjection method, when properly controlled, is a reliable and practical one. While it does not possess the mathematical exactness of the gas analysis, the conclusions drawn from its results are identical with those of the latter in regard to the course of the two caval streams through the heart. 464 HOWARD B. KELLOGG
leaving the heart will cause dilatation, especially of the atria,
 
a slowing of the rate, and contractions of a more forceful
 
character. Further, the results seldom showed exactly the
 
same amount of starch in the two sides of the heart and the
 
Variations were not constant in any one direction. Had stasis
 
and churning occurred, one might expect the samples from
 
the two sides of the heart to contain equal quantities of
 
starch. On the contrary, the inconstant Variation obtained
 
seems to indicate a slight variable error due to different
 
degrees of mixing in the heart itself.
 
  
Interference to heart action resulting from the introduction of sharp needles for the purpose of withdrawing samples
+
==Conclusions==
can hardly be a serious objection, since the heart continued
 
to beat regularly and normally and the samples were secured
 
within two or three contractions after the needles were
 
inserted.
 
  
Too rapid a rate of injection of the starch suspensions might
+
After injecting India ink and starch suspensions into the external jugular and umbilical veins of living pig and dog fetuses,,direct observation and quantitative determinations prove that the blood of the superior and inferior venae cavae of fetal mammals is thoroughly mixed in the right atrium and then distributed to the two ventricles.
introduce considerable error. As has been pointed out in
 
the discussion of the results obtained with dog fetuses, too
 
rapid injection into the umbilical Vein may result in more
 
than the normal amount of inferior vena cava blood passing
 
through the foramen ovale to the left side of the heart.
 
  
In any series of injections where such technique was employed throughout there undoubtedly would be a constant
+
The foramen ovale is the same relative size in the later stages of gestation as in the early ones; the fetal circulation does not approach the adult type before birth.
predominance of starch found in the left heart. This occurred in the dog series only. It might likewise be assumed
 
that too rapid injection into the superior vena cava would
 
result in a greater quantity of starch going to the right heart.
 
  
In the present series of experiments none of the superior
+
The early rapid development of the head, liver, and upper extremities as compared to the growth of the rest of the body does not depend upon a superior oxygen supply.
Vena-cava injections was made rapidly, and since there was
 
no predominance in favor of the right heart, it seems certain
 
that these injections were not too rapid.
 
  
Since in the dog series only, in which injection was purposely much faster than in the pig series, was there a predominance in the amount of starch found in one side of the
+
Circulatory efiiciency in the mammalian embryo apparently rests on a relatively large amount of swiftly flowing blood and upon a generous factor of safety in its oxygen.
heart, it follows that the rate of injection, if properly controlled, is not necessarily a source of great error.
 
BLOOD FLOW THROUGH THE MAMMALIAN HEART
 
  
Differences in the negative pressure applied to the two
+
==Literature Cited==
needles might cause the blood to be sucked by way of the
 
foramen ovale from the side of the heart of least negative
 
pressure to the side containing the needle of greatest negative pressure. This was overcome by the use of the Y tube
 
connected to the two needles, as already described (p. 452).
 
That the samples obtained simultaneously from the two sides
 
of the heart were approximately always equal in amount is
 
good and sufficient proof that this did not occur.
 
  
It is evident that the above objections apply chiefly to the
+
BORN, G. 1899 Beitriige zur Entwicklungsgeschichte des Saugetierherzens.
quantitative results and, to a much less degree, to the ocular
 
observations of the ink and starch injections.
 
  
Even though the theoretical objections to the injection
+
Arch. f. mik. Anat., Bd. 33, S. 368, 369.
method seem to have been sufficiently overcome in its practical
 
application, fear that some might still be skeptical has led
 
to a search for a new and more refined quantitative means
 
of approach.
 
  
The development of the Van Slyke micro gas analysis of
+
DALTON, J. C. 1884 Doctrines of the circulation. Lea’s Son & Co., Philadelphia. -
blood for its oxygen and carbon-dioxide content has ideally
 
satisfied this demand. This method makes it possible to
 
determine with chemical exactness the amount of oxygen and
 
carbon dioxide present in the blood of the various vessels of
 
the fetus.
 
  
The results and technique of gas analysis will appear in
+
HARVEY, W. 1628 Anatomical dissertation on the movement of the heart and blood in animals. Privately reproduced from the original edition printed at Frankfort-on-the-Main in 1628. With a translation and memoir for G. Moreton, 42 Bur-gate St., Canterbury, 1894.
a separate publication. It may be stated here that the results
 
of gas analysis have shown beyond all doubt that the starchinjection method, when properly controlled, is a reliable and
 
practical one. While it does not possess the mathematical
 
exactness of the gas analysis, the conclusions drawn from
 
its results are identical with those of the latter in regard
 
to the course of the two caval streams through the heart.
 
464 HOWARD B. KELLOGG
 
  
CONCLUSIONS
+
HOOKER, D. R. 1921 Evidence of functional activities on the part of the capillaries and venules. Physiol. Rev., vol. 1, pp. 112-139.
  
After injecting India ink and starch suspensions into the
+
KILIAN, H. F. 1826 fiber den Kreislauf des Blutes im Kinde, welches noch nicht geathmet hat. Karlsruhe, p. 200. (Loc. cit. Pohlman, 1909 b, p. 80.)
external jugular and umbilical veins of living pig and dog
 
fetuses,,direct observation and quantitative determinations
 
prove that the blood of the superior and inferior venae cavae
 
of fetal mammals is thoroughly mixed in the right atrium
 
and then distributed to the two ventricles.
 
  
The foramen ovale is the same relative size in the later
+
MERY 1645-1722 (Op. cit. Pohlman, 1909 b, p. 79).
stages of gestation as in the early ones; the fetal circulation
 
does not approach the adult type before birth.
 
  
The early rapid development of the head, liver, and upper
+
POHLMAN, A. G. 1907 The circulation of the blood through the fetal heart. Johns Hopkins Hosp. Bull., vol. 18, pp. 409-412.
extremities as compared to the growth of the rest of the body
 
does not depend upon a superior oxygen supply.
 
  
Circulatory efiiciency in the mammalian embryo apparently
+
1909 The fetal circulation. Amer. Med., Burlington, Vt., vol. 4, pp. 317-320.
rests on a relatively large amount of swiftly flowing blood
 
and upon a generous factor of safety in its oxygen.
 
  
LITERATURE CITED
+
1909b The course of the blood through the heart of fetal mammale, with a note on the reptilian and amphibian circulation. Anat. Rec., vol. 3, pp. 75-109.
  
BORN, G. 1899 Beitriige zur Entwicklungsgeschichte des Saugetierherzens.
+
1916 The function of the foramen ovale. Interstate Med. Jour., vol. 23, pp. 105-124.
  
Arch. f. mik. Anat., Bd. 33, S. 368, 369.
+
PREYER, W. 1883-1885 Specielle Physiologic des Embryo. Th. Griefen’s Verlag (L. Fernau), Leipzig, 8. 79-88, Tafel 5. r
 
 
DALTON, J. C. 1884 Doctrines of the circulation. Lea’s Son & Co., Philadelphia. -
 
HARVEY, W. 1628 Anatomical dissertation on the movement of the heart and
 
blood in animals. Privately reproduced from the original edition
 
printed at Frankfort-on-the-Main in 1628. With a translation and
 
memoir for G. Moreton, 42 Bur-gate St., Canterbury, 1894.
 
 
 
HOOKER, D. R. 1921 Evidence of functional activities on the part of the capillaries and venules. Physiol. Rev., vol. 1, pp. 112-139.
 
 
 
KILIAN, H. F. 1826 fiber den Kreislauf des Blutes im Kinde, welches noch
 
nicht geathmet hat. Karlsruhe, p. 200. (Loc. cit. Pohlman, 1909 b,
 
p. 80.)
 
 
 
MERY 1645-1722 (Op. cit. Pohlman, 1909 b, p. 79).
 
  
POHLMAN, A. G. 1907 The circulation of the blood through the fetal heart.
+
REID, J. 1835 Injection of the vessels of the fetus to show some of the peculiarities of its circulation. Edinburgh Med. and Surg. Jour., vol. 43, pp. 11~13. 1835 Additional observations, Ibid., vol. 43, pp. 308—310.  
Johns Hopkins Hosp. Bull., vol. 18, pp. 409-412.
 
  
1909 The fetal circulation. Amer. Med., Burlington, Vt., vol. 4,
+
SA_BA'I‘IER., RAPHAEL B. 1791 Traité complet dhénatomie, T. 2, p. 493. (Loc. cit. Pohlman, 1909b, p. 80.) SENAC’ 1773 (Op. cit. Pohlman, 1909b, p. 79.)
pp. 317-320.
 
  
1909b The course of the blood through the heart of fetal mammale, with a note on the reptilian and amphibian circulation. Anat.
+
SERVETUS, M. 1553 Christianismi Bestitutio, p. 170. (Loc. cit. Dalton, p. 115.)
Rec., vol. 3, pp. 75-109.
 
  
1916 The function of the foramen ovale. Interstate Med. Jour.,
+
VESALIUS, ANDREAS 1543 De Humani Corporis. Liber 4, Cap. 15. (Loc. cit. Dalton, p. 108.)
vol. 23, pp. 105-124.
 
  
PREYER, W. 1883-1885 Specielle Physiologic des Embryo. Th. Griefen’s
+
WOLFF,_ C. F. 1778 De foramine ovali ejusque in dirigendo sanguinis matro. Observ. novae. Nov. comment. Scient. Petropolit 20. (Loc. cit. Pohlman, 1909b, pp. 78-80.)
Verlag (L. Fernau), Leipzig, 8. 79-88, Tafel 5.
 
r
 
  
BLOOD FLOW THROUGH THE MAMMALIAN HEART
+
ZIEGENSPECK, R. 1882 Welche Veriinderungen erffihrt die foetale Hei-zth§tig— keit regelnfalssig durch die Geburt. Inaug. diss., Jena. 1884 P1-eyer’s Physiologie des Embryo, S. 596-607. 1902 fiber Foetal Kreislauf. Miinchen. 1905 Die Lehre Von der doppelten Einmiindung der unteren Hohlvene in die Vorhofe des Herzens und der Autoritéltsglaube. Sammlung klinischer Vortrige (Ser. 14, Heft 11), No. 401.
  
REID, J. 1835 Injection of the vessels of the fetus to show some of the
+
{{Footer}}
peculiarities of its circulation. Edinburgh Med. and Surg. Jour., vol.
+
[[Category:Historic Embryology]][[Category:Heart]][[Category:1920's]]
43, pp. 11~13.
+
[[Category:Draft]]
1835 Additional observations, Ibid., vol. 43, pp. 308—310.
 
SA_BA'I‘IER., RAPHAEL B. 1791 Traité complet dhénatomie, T. 2, p. 493. (Loc.
 
cit. Pohlman, 1909b, p. 80.)
 
SENAC’ 1773 (Op. cit. Pohlman, 1909b, p. 79.)
 
SERVETUS, M. 1553 Christianismi Bestitutio, p. 170. (Loc. cit. Dalton, p. 115.)
 
VESALIUS, ANDREAS 1543 De Humani Corporis. Liber 4, Cap. 15. (Loc.
 
cit. Dalton, p. 108.)
 
WOLI"F,_ C. F. 1778 De foramine ovali ejusque in dirigendo sanguinis matro.
 
Observ. novae. Nov. comment. Scient. Petropolit 20. (Loc. cit.
 
Pohlman, 1909b, pp. 78-80.)
 
ZIEGENSPECK, R. 1882 Welche Veriinderungen erffihrt die foetale Hei-zth§tig—
 
keit regelnfalssig durch die Geburt. Inaug. diss., Jena.
 
1884 P1-eyer’s Physiologie des Embryo, S. 596-607.
 
1902 fiber Foetal Kreislauf. Miinchen.
 
1905 Die Lehre Von der doppelten Einmiindung der unteren
 
Hohlvene in die Vorhofe des Herzens und der Autoritéltsglaube.
 
Sammlung klinischer Vortrige (Ser. 14, Heft 11), No. 401.
 

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Kellogg HB. The course of the blood flow through the fetal mammalian heart. (1928) Amer. J Anat. 42(2): 443-

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This historic 1928 paper by Kellogg describes development of blood flow through the heart.



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=The Course of the Blood Flow Through the Fetal Mammalian Heart

Howard B. Kellogg


Department of Anatomy, Northwestern University Medical School

Three Figures

  • Contribution no. 130. Submitted as one section of a thesis in partial fulfillment of the requirements of Northwestern University for the degree of Doctor of Philosophy.

Introduction And Historical

There is little exact information regarding the physiology of the fetal circulation in mammals. Two major problems present themselves: 1) the circulation of blood through the fetal heart; 2) the nature of placental exchange and the gaseous content of the maternal and fetal vessels. It is with the first of these problems that the ‘present report is concerned, Whereas the second will appear in a separate publication.


The history of the dispute concerning the blood flow within the fetal heart and its quantitative distribution dates from the beginning of the fourth century. It has been reviewed so thoroughly by Pohlman (’09 b) that only an outline and analysis of the more important phases are necessary.

1. Early discoveries

Galen (about 300 AD.) gave the first adequate description of the fetal heart. He described the foramen ovale and the ductus arteriosus and mentioned their fates after birth. He further commented on the remarkable provisions of nature in requiring but a small amount of blood to flow through the lungs before their respiratory function began. Wliile Galen’s account of the anatomy of the fetal heart was quite accurate, he reversed the course of the blood and described it as flowing from the aorta to the lungs by means of the ductus arteriosusi


At this time there was much mystery concerning the adult circulation, and Galen further erred in assuming that the blood somehow passed through, the ventricular septum on its course from the right ventricle to the left. Vesalius (1543), some time later, rightly questioned the teachings of Galen on this point.


Servetus (1553) made the important discovery that the blood, after passing through the lungs, is of a bright red color. It is possible that he might have interpreted this observation in terms of the pulmonary and systemic circulations had it not been for his untimely death at the stake as a penalty for his alleged radical teachings. Servetus also recognized the foramen ovalein the fetal heart.

2. The Wolff-Ziegenspeck School

In the middle of the eighteenth century, Wolff (1778; Pohlman, ’09 b, pp. 79, 80) thought he had found a new anatomical relationship between theforamen ovale and the inferior Vena cava. He pictured the inferior Vena cava entering the two atria on their posterior walls so that the limbus of the foramen ovale cut the caval orifice into two openings. On the basis of these relations, he taught that the inferior caval blood stream was split, half going to each atrium, and the effect being the same as if there were, indeed, two inferior venae cavae, one to each atrium. This conception means that the pulmonary return must equal the superior caval return, otherwise the circulation would be unbalanced.

Ziegenspeck.(’81, ’05) corroborated Wolff’s findings and likewise believed that the inferior caval stream was divided by the limbus of the foramen ovale. The following diagram represents Pohlman’s (’09 b, pp. 88, 89) quantitative interpretation of Ziegenspeck’s views:

Lungs &———-——-————%—> Pulmonary return i


Right ventricle 1} Left ventricle 1} . \ /, Ductus arteriosus } Left atrium i \- /' Aorta descendens %—————-——>‘ Vena cava inferior §


Pars communis aortae & Right atrium

Left ventricle 1} Right ventricle %

Aa. carotis et subclavius :} —-> Vena cava superior

These deductions were based upon a series of thirty—six injections into the‘ umbilical veins of dead pig fetuses and upon the analysis of a carefully measured calibration of the cardiac vessels of thirty—three fetuses. The injections indicated that one-half of the inferior caval stream goes to each atrium, and there are no objections to‘ such conclusions. It is Ziegenspeck’s interpretation of these results that seems to be at fault. V

Pohlman shows that Ziegenspeck’s Qonclusions are incorrect, for the reason that the laws of hydrodynamics do not permit vessels of the size listed to deliver the amounts of blood the arrangement calls for. Pohlman also makes the following criticism:

In any event the results will show that measurements of this character are valueless because We must grant that:

  1. The lumina are exactly circular.
  2. The vessel elasticity must be equal.
  3. The expansion of these vessels must be equal in all directions.
  4. The intrinsic vessel resistance must be the same.
  5. The capillary resistance in all vessels must be equal or known.
  6. The quantity of blood expelled by the two sides of the heart must be the same and the pressure exacted equal. T
  7. The vessels must undergo no particular change after death and fixation.

Hooker’s investigations (’21), in which he shows that the capillary resistance of a given capillary bed is constantly changing, makes it impossible to accept proposition no. 5, even though the area supplied by a given vessel might be proportional to its carrying capacity. The marked difference in the histological structure of a vein and an artery makes it unsafe to assume that there is no change after death and fixation, or, in case of a change, that it would have been proportional to the carrying capacity of the vessel. Pohlman further points out that Ziegenspeck entirely omitted the following:

  1. The azygos circulation.
  2. The coronary circulation.
  3. The lymphatic return to the superior Vena cava.

3. The Sabatier School

Sabatier (1798) published his account of the blood flow through the fetal heart, and it is the prevalent one to—day. He describes the two caval streams crossing in the right atrium without mixing, the blood from the inferior Vena cava being directed through the foramen ovale by the eustachian valve to the left side of the heart and that from the superior vena cava passing through the tricuspid orifice to the right ventricle. T

It is evident that such an arrangement would supply the head and upper extremities with blood richer in oxygen than that received by the rest of the body. The more rapid development of the head, upper extremities, and liver has been explained on the basis of a better blood supply to these parts.

Kilian (1826) believed that mixing of the caval streams occurs to some extent,_but he described an aorta cerebralis, which carried the best blood to the brain, and an aorta abdominalis, which carried the poorer blood to the rest of the body.

Reid (’35) performed three injection experiments upon dead human fetuses. The superior Vena cava was injected with a yellow mass and the inferior Vena cava with a red mass. No two of these experiments agreed. He accepted the results of one injection which did not show any mixing of the two fluids, and remarked that, of the remaining two, one was injected in the wrong directionand the third was poorly handled. He thus satisfied himself that the head and upper extremities receive fresher blood than does the rest of the body. The objections to such work seem too great to require much comment. First, the substances used must have had a viscosity and specific gravity several times that of blood, or else they would have mixed to some extent before he could have opened the heart. Secondly, the heart, being dead, must have been more or less rigid, whereas the living heart undergoes dilatation while being filled. - He agrees that undoubtedly some organs do not require an especially rich blood supply for rapid development, but that, since the brain in the adult is very sensitive to minute changes in its oxygen supply, so must it be in its growth. He further states:

And lastly when we consider the entrance of the two cavae themselves, the superior passing downwards and forwards, the inferior upwards and backwards, and to add to this the thick upper margin of the foramen ovale, we further perceive that the blood, passing down the cava superior must fall directly into the right auricle, to the left side of the Eustachian valve, and thus fill the right ventricle.

To fulfill these conditions it is necessary to suppose that the fetus is kept in an upright position, or else the blood could not fall from the superior vena cava above to the right ventricle below. Pohlman ( ’07, p. 409), in his review of the Sabatier conception of the fetal circulation, raises these objections: .

A critical examination of the theory, which by the way is the prevalent one at this time, shows it to be physically impossible, morphologically inaccurate, and developmentally unnecessary. Physically impossible, because it would entail a distinct crossing of two currents under equal pressure in a distending chamber. Morphologically inaccurate, as Born has pointed out, in that no such. arrangement is found in the sauropsidian embryo, or even more strikingly in the human embryo, where the leg buds, once they appear, develop more rapidly than the arm buds when on the Sabatier principle the reverse should be the case. Developmentally unnecessary in that a number of organs grow rapidly from anlage to relatively large size without being vascularized (kidney, testes).

4. The Harvey-Pohlmcm School

The rather obscure theory of the fetal circulation given by Harvey (1628) seems, even to-day, to be correct in the main. Harvey formulated this conception after his epochal discovery of the adult pulmonary circulation andia careful study of the anatomy of the fetal heart. As Pohlman (’O9 b, p. 79) pointed out, the terminology used by Harvey has led to various interpretations. Pohlman’s careful translation of Harvey’s original description shows that Harvey believed the two caval streams to mix in the right atrium before passing to the ventricles.

For a time Mery (1645-1722) succeeded in overshadowing Harvey’s work with his idea that the fetal blood flows from the left to the right atrium by means of the foramen ovale. However, Senac (1773), on repeating Mery’s injection experiments, proved them to be in error.

Pohlman. (’O9 b), utilizing pig fetuses, did the first work on living animals. He first determined the capacities of the two ventricles and found them to be equal. This was done by slipping a ligature around the atrioventricular sulcus and drawing it tight at the end of the atrial diastole. The blood in each ventricle was then measured. Next, he demonstrated that the pressures in both ventricles were equal by introducing identical pipettes into the two ventricles at the same time. The blood mounted equally in both pipettes. He concluded that, since there was no oscillation of the blood at the time of diastole, there could be no suction or aspiration effect due to the expanding heart. The latter had been assumed to be true for some time, but had never been proved. ,

Pohlman then made a series of injection experiments, the technique of which will be found on page 451. He injected a suspension of cornstarch into the chosen vessel and withdrew equal amounts of blood from each ventricle at the same time. Seventeen injections were forced into the umbilical veins of pig fetuses. The blood samples drawn from the ventricles were arranged in pairs for the purpose -of comparison. In five pairs neither tube contained any starch.


Since he opened the thorax after the injections were made, it is probable that in these cases the rapid fetal heart beat had already passed the starch through before it could be recovered. Twelve pairs showed an equal volume of starch in the blood from each ventricle, and this was confirmed by rough microscopic examination.

Pohlman next succeeded in making seven injectionsinto the superior vena cava, although it was difficult to avoid serious hemorrhage. From these tests he obtained four pairs of tubes with equal amounts of starch inweach tube. Two pairs had a difference of over 50 per cent, «but there is no. record as to whether the results were consistent. One pair contained no starch. He further made simultaneous injections of colored starch into the superior vena cava and an uncolored starch into the inferior vena cava. After six such injections, the blood recovered from each ventricle was first diluted in acetic acid to destroy the erythrocytes, and then compared. Both colored and uncolored granules Occurred in each sample. Quantitative counts could not be made for the iodine-potassium iodide used to stain the colored granules diffused too rapidly into the uncolored ones.

From these results Pohlman concluded that the caval streams do mix in the right atrium and that the foramen ovale does form a communication between the right and left atria, instead of being placed so as to split the blood from the inferior vena cava into two parts. He further declares that the blood to the head and upper extremities can be of no better quality than that to the rest of the body, and hence the more rapid development of the upper body does not result from a richer blood supply.

5. The present status of the problem

Inspection of many standard text—books of anatomy, embryology, and Obstetrics, since the time of Pohlman’s publication, shows a division of opinion between the Sabatier and Harvey—Pohlman theories. The former is favored by a large majority, several texts being non-committal in judg450 HOWARD B. KELLOGG

ment, and a few advocating the Harvey—Pohlman view. The Ziegenspeck-Wolff conception, based chiefly upon Ziegenspeck’s interpretation of his injections of dead pig fetuses and the calibration of the vessels of the heart, which since have been shown to be unreliable, is no longer considered seriously.

Regarding the two rival theories, it appears that the only experimental evidence in support of the Sabatier scheme is that of Reid, yet his work is practically valueless, because, of the three injections made upon dead human fetuses, no two agreed. The anatomical evidence supporting this view is based upon the position of the eustachian valve. This, however, does not seem to be adequate, for although in a fixed, motionless heart the valve might be capable of directing all of the inferior caval blood through the foramen ovale, nevertheless, it must lose most of its positional advantage in the distending heart. The supposed morphological necessity of such a condition may be disregarded, since Born (’89) and Pohlman (’07,"p. 409) have argued convincingly from analogy that the more rapid development of the head and upper extremities does not necessarily depend upon a superior blood supply. On the contrary, it can be urged that the anatomical relations may be interpreted equally as evidence in support of either the Sabatier or Harvey-Pohlman theory.

The work of Pohlman, although highly suggestive and unique in its employment of experimentation on living animals, has lacked conviction, because his conclusions were based upon relatively few experiments. There is also a doubt as to their exactness, due to the theoretical disturbances of the circulation brought about by injecting a foreign substance into the heart and then piercing the heart to remove it. For these reasons and with the hope of gaining more precise information as to the degree of blood admixture in the heart, a program of experimentation was outlined. In this it was first decided to repeat, expand, and, if possible, improve on Pohlman’s type of experiments. It is with these results that the present paper is concerned. In a subsequent contribution more refined quantitative determinations, using the methods of gas analysis which eliminate some of the more serious theoretical objections, will be reported.

I wish to express my great appreciation to Dr. L. B. Arey for suggesting this problem and also for his constant assistance during the work. The generous cooperation of Swift & Company, Chicago, expedited the work.

Experimental

Starch and ink injections

The method of starch injections, as used by Pohlman, with some changes in technique was employed and a series of over 200 observations has been obtained.

Materials and methods. This type of experimentation is not dependent upon a normal placental exchange, and therefore permits the choice of pig fetuses as material. The large size and the availability of these fetuses is a distinct advantage in such work. In addition, one pregnant dog was secured and used while the placental circulation of both mother and fetuses was intact.

The pig experiments were done on the killing floor of Swift & Company, Chicago. Operative conditions were not the best, but the abundance of material compensated for any inconveniences. Fifteen to thirty minutes after killing, the sows were opened, the uterus cut at the cervix and handed to the experimenter. This lapse of time and the drainage of blood from the sow had a material effect upon the procural of suitable living material. About one uterus out of four of those large enough to use contained fetuses that maintained a sufficiently vigorous heart beat; the only blood samples retained were those taken from pigs whose hearts continued to beat at least ten times after the blood was withdrawn. When received, the uterus was opened at once along its least vascular border and the fetus removed with a minimum disturbance to the placenta and fetal circulation. It is possible to cut away the ventral thoracic wall and open the pericardium with but slight hemorrhage. In this manner the heart is made freely accessible for rapid observation and blood sampling before beginning the experimental procedure. It is important to eliminate the possibility of error through delay or by mechanical violence in exposing the field of operation. ‘

The type of experimentation employed was the injecting of suspensions into the superior and inferior venae cavae and then either observing the visible effect on the two halves of the heart or making controlled computations of the contained blood-suspension mixture. The first result is qualitative, but possesses the merit of furnishing ocular proof without the introduction of additional manipulative factors; the second is quantitative, and, properly controlled, affords a basis for definite mathematical comparisons. .

The technique of the direct-observation experiments was simple. Suspensions of India ink or of 10 per cent cornstarch in physiological salt solution were introduced into the selected vessel by means of a hypodermic syringe, whereupon the resultant color change in the heart was noted.

The objective of the quantitative tests was to obtain from many experiments a more accurate estimate of the extent of admixture of the two caval streams within the right atrium. This was to be done by introducing starch into a vein and then making counts of ‘the granules obtained from samples of blood withdrawn simultaneously from the two ventricles. Further checks were to be secured by comparison of the amounts of starch which settled out differentially from samples of blood allowed to stand in narrow tubes.

A 10 per cent starch suspension was introduced into the selected vessel by means of a hypodermic syringe and three to ten seconds later equal quantities of blood were withdrawn from the two ventricles with identical pipettes. It was necessary to use caution in the rate and amount of the injection to avoid excessive pressure within the vessel. The pipettes used were small pieces of glass tubing, held together by rubber bands, to which no. 20 needles were attached. The opposite ends of the pipettes were connected to a Y-tube by means of rubber tubing. By sucking gently on the stem of the Y, a common negative pressure was imparted to each needle, and equal volumes of blood were usuallyobtained. Samples with appreciable differences in volume were rejected. The two samples thus obtained were then drained into paired vials, each containing ‘two drops of potassium oxalate. This amount of oxalate prevented clotting and was not sufficient to introduce any significant error in the results.

When making a starch count, the blood was diluted one hundred times in a solution which contained a small amount of potassium iodide and iodine; the starch granules stained well with the iodine. Counts were made, using the chamber regularly employed in clinical blood computations. It was found that the specific gravity of starch granules is so high that they do not always spread evenly, but may tend to settle out on the slide near the point where the drop was emitted from the mixing pipette. To equalize this tendency, four counts were made from each sample, and the average value then used.

When blood containing starch is allowed to settle undisturbed, the starch granules, because of their greater specific gravity, occupy a bottom layer; next come the cellular ele -ments, whereas the highest stratum is of clear serum. This

differential sorting is preferable to separation by centrifuging. The volume of blood usually obtained in a single sample is 1 cc.,. but this amount is not sufficient to allow comparisons of the settled starch in ordinary centrifuge tubes. To overcome this difficulty, each tube received an equal quantity from eight to twelve corresponding pairs of samples. Composite columns of blood, 5 to 6 cm. in height, were thus obtained.

On the contrary, individual tubes were also prepared from glass tubing with a3-mm. bore. These tubes gave a column of blood from a single sample ‘sufficiently high for the purpose of comparison. A large drop of mercury placed in the bottom of each tube produced a surface upon which the starch settled; this eliminated errors due to unequal curvatures at the sealed ends.

Observations. 1. Direct inspection of heart. Careful observation of the fetal pig heart showed that almost immediately after an injection of the starch suspension into the umbilical or external jugular vein both ventricles blanched. The apices of the two ventricles, being thinner than the rest, showed this decoloration very markedly. Similarly, when India ink was introduced into the veins, it was obvious that both ventricles became equally black at once. These injections were repeated on about 125 fetuses of various ages, and in every instance the discoloration occurred equally in both ventricles at the same moment. These observations, while not primarily of a quantitative value, constitute definite evidence proving beyond a doubt that the two caval streams do mingle in the right atrium, whereupon both ventricles receive mixed arteriovenous blood. They are especially important, because they involve no subsequent disturbance of the heart.

After the starch injections are made, the heart usually continues to beat at its regular rate, but frequently the heart is accelerated. This augmentation is probably due to the warmth of the starch solution or to a slight increase in pressure. Inthe case of the ink, which is toxic, the heart usually stopped within three to ten pulsations after the fluid reached the ventricles.

Similar observations were made on five living dog fetuses, delivered under ether anaesthesia. The maternal and fetal circulations continued normally. The results from injections into the umbilical vein were identical with those obtained with pigs. The importance of such direct observations cannot be overemphasized.

2. Quantitative determinations. A. Results on pigs. a. Quantitative counts. Starch granules were counted in selected unit areas of the ruled chamber and the totals from ten fetuses summated. Such grand counts from pig fetuses that had received injections into their umbilical veins gave a ratio of 253 in blood withdrawn from the right ventricle to 293 in that from the left. On the basis of these results alone, the inference is that the left ventricle received 16 per cent more blood from the inferior vena cava than did the right (but see p. 458).

12. Volume comparison. Three sets of composite tubes, each containing equal amounts from eight, nine, and twelve paired samples,’ respectively, were prepared from blood taken after the fetuses had received starch injections into the umbilical veins. From these a column of starch about 53 inch high Settled out. There was no appreciable difference in the amount of starch representing the right and left ventricles.

Thirty—three paired sets from umbilical—vein injections and thirty sets from external jugular-vein injections were next prepared. Each blood sample was placed in an individual narrow tube (compare p. 456). These occasionally showed a small difference in the amount of starch representing the right and left ventricles, but such variation was not consistently in one direction and the series as a whole essentially balanced. (Figures 1 to 3 illustrate well the type of result obtained from such injections.) The small bore of the indi~ vidual tubes made it difiicult always to introduce the complete sample into the tube. For this reason, the starch columns must in each instance be compared with the height of the corresponding column of blood. It is evident that in most paired samples the quantity of starch in each tube was proportionally the same.

B. Results on dogs. The dog fetuses were too small (although well toward the end of gestation) to attempt ex_ternal jugular-vein injections. Hence, the five fetuses were injected through the umbilical veins only and the samples placed in individual sets of small tubes. There was more variation in the corresponding tubes of this series (fig. 3), the ratio between the right and left ventricle samples ranging from 10:11.7 to 5228.5, respectively; the average being 25.3): 33, respectively. Nevertheless, this difference is probably capable of explanation on the basis of technical procedure rather than representing a natural relation (p. 458).


Fig. 1 A series of ten pairs of tubes containing blood taken simultaneously from the right and left ventricles of pig fetuses after the injection of a starch suspension into the umbilical vein.


Fig. 2 A series of ten pairs of tube containing blood taken simultaneously from the right and left ventricles of pig fetuses after 3. starch suspension was injected into the external jugular vein.


Fig. 3 A series of five pairs of tubes containing blood taken simultaneously from the right and left ventricles of dog fetuses after the injection of a starch suspension into the umbilical vein.

EXPLANATION or FIGURES 1, 2, AND 3

As stated in the text, it was impossible always to fill the 3-mm. tubes to the same level. Hence, for purposes of ready comparison, all columns of blood in the accompanying illustrations have been reduced to the same height, and the starch columns have been similarly corrected and reproduced in their exact ratios. . '

The letter L and R at the bottom of the tubes indicate that the blood was taken from the left or right ventricle. The solid block at the bottom of the tube represents the mercury put in to give an even surface for the starch to settle upon. The short white columns above the block repreent the sedimented starch, and the stippled strata correspond to the supernatant blood. 458 HOWARD 13. KELLOGG

Discussion

The ocular observations of the starch and ink injections show clearly that the two caval streams do mix in the right atrium, while the starch counts and the sedimentation experiments are a quantitative proof that the two sides of the heart receive blood of approximately the same character.

The results, obtained in the pig series of over 100 injections and 125 direct observations of the heart, show some discrepancies, but they are not great and could, no doubt, be eliminated if a better control of operative conditions were possible (compare p. 451).

The heart beat of the fetal dogs was so rapid, due to their normal uninterrupted oxygen supply, that it seemed advisable to make the injection much faster than usual to prevent the starch from being pumped through the heart before the samples could be withdrawn. In doing this there is little doubt that the pressure in the inferior vena cava was raised considerably above normal. Since the foramen ovale is in a more direct line with the inferior caval blood stream than is the tricuspid orifice, an increased pressure in the inferior cava would. tend to drive more than the usual amount of its blood through the foramen ovale. While these results showed the greatest variation of any in the present series, they nevertheless afford very important evidence in support of the Harvey-Pohlman theory, since they are the first obtained on animals in which both the maternal and fetal sides of the placental circulation were intact and the other general conditions approached normality.


The small percentage in favor of the left side of the heart receiving more pure blood, as indicated by the results obtained from the starch counts, may well be within the error introduced from the failure of the starch granules to spread evenly on the counting chamber. These results were all from the earlier injections, and again it is likely that the then undeveloped technique in controlling. the rate- of injection would account for more of the inferior caval stream going through the foramen ovale.


Pohlman had difficulty in obtaining starch in all of the samples; seven out of twenty-nine sets contained no starch at all. This undoubtedly was due to the fact that he delayed too long his Withdrawal of the samples by opening the thorax after making the injections. By reversing these procedures in the present investigation, but three sets showing no starch were obtained in over a hundred samples. Pohlman also found great difliculty in opening the thorax sufficiently high to expose the superior vena cava without severe hemorrhage ensuing; additional hemorrhage occurred as Well when the needle was Withdrawn after the injection had been made into the superior vena cava. By using the external jugular vein as an avenue to the superior cava, it was not necessary to open the thorax so high, and there was also no hemorrhage after the needle was "Withdrawn from, the small vein. The small size of the external jugular vein made only the larger pigs of value for this injection; many experiments Were rejected before the recorded numbers of successful injections were obtained.

The direct observations of the heart While starch and ink injections were made is so simple and reliable, for it eliminates the possibilities of induced error resulting from the trauma of pipettes, that it cannot be overemphasized as a critical method of attack. .

It is stated by some authorities that, as the fetus nears the end of the gestation period, the foramen ovale and ductus arteriosus become proportionally smaller and smaller with the concomitant increase in the blood flowing through the lungs. If this were true, the fetal circulation would approach the adult type before birth. To gain information on this point, complete records were kept of the lengths of all pig fetuses. The pig fetuses varied from 6 to 14 inches in length. Pig fetuses 14 inches in length are nearly at term.

It was not possible to correlate any difference in the proportion of caval blood going to each ventricle with increasing size. A careful examination of a considerable number of fetal hearts seems to show that the foramen ovale maintains its relative size throughout fetal life, but that the two atrial septa (primum and secundum) do become much larger in the late stages of gestation. Yet, while the septa do more nearly overlap, they are so placed that the blood may pass freely from the right to the left atrium until such time as there is an increased pressure in the left atrium to hold them in apposition. This, however, cannot take place until the respiration at birth forces a greater amount of blood through the lungs.

It will be remembered that Reid furnished the only experimental support to the popular Sabatier theory, but that his results are too meager and uncritical to be of any real value (p. 446); at best, the Sabatier conception is a mere philosophical argument, based on the supposed advantages that would accrue from a differential segregation of pure and impure blood.

On the contrary, the results presented in the present investigation agree exactly with those of Pohlman and attest to the fundamental correctness of the Harvey—Pohlman view. The fact that the present results were obtained from a large series of animals and several methods of attack (i.e., ocular observation, starch counts, and sedimentation of starch on living fetuses, some of which had normal placental relations) makes them much more trustworthy than those of but one method. If there is any difference in the quality of blood furnished to the different parts of the body, the amount is quantitative and not significant.

To those who obtain mental satisfaction from fitting supposedly advantageous mechanisms to physiological ideals, the Harvey—Pol1lman theory may be disappointing. Yet it is by no "means certain that there is any necessity in "maintaining a difference in the quality of blood distributed to the various parts of the body. Circulatory efficiency in the mammalian embryo doubtless depends jointly on the relatively large quantity of swiftly moving blood and on the large factor of safety in the oxygen supply.


At the outset it was recognized that the injection of starch granules into the venae cavae as a method of attacking this problem has certain theoretical shortcomings. Objections to this type of experimentation apply especially to any quantitative deductions that may be made.

Possible errors might be expected to result from:

  1. The introduction of a foreign substance into the blood stream.
  2. Blockage by the starch granules of the capillary beds beyond the heart, which would result in stasis and churning of the blood within the heart.
  3. The interference with heart action by piercing it when drawing samples.
  4. Injection of starch suspensions under such great pressure that the equilibrium of the two caval streams entering the right atria would be disturbed.
  5. Withdrawing samples from the two ventricles under unequal negative pressures, which likewise would change the natural circulation within the heart.


The objection to the introduction of a foreign substance into the blood stream can be minimized if the material used is not toxic and the viscosity and specific gravity are not at too great variance with that of normal blood. The starch suspensions in physiological saline are not toxic. It is true the viscosity of the solution is somewhat less than that of blood and the specific gravity of starch granules is greater than that of blood corpuscles. However, in a blood stream that is moving at a normal rate these diiferences are probably not large enough to have noticeable effect.

The possibility of vascular stasis resulting from blockage of the capillary bed beyond the heart'seems to be the most serious feature of this type of experimentation. Undoubtedly, stasis in the heart would result in churning of the blood and a consequent admixture through the foramen ovale of the blood in the two sides of the heart. That this did not occur seems evident by the fact that no marked change in the heart rate nor in the amplitude of contraction and dilatation occurred. It is well recognized that a sudden blockage of blood leaving the heart will cause dilatation, especially of the atria, a slowing of the rate, and contractions of a more forceful character. Further, the results seldom showed exactly the same amount of starch in the two sides of the heart and the Variations were not constant in any one direction. Had stasis and churning occurred, one might expect the samples from the two sides of the heart to contain equal quantities of starch. On the contrary, the inconstant Variation obtained seems to indicate a slight variable error due to different degrees of mixing in the heart itself.

Interference to heart action resulting from the introduction of sharp needles for the purpose of withdrawing samples can hardly be a serious objection, since the heart continued to beat regularly and normally and the samples were secured within two or three contractions after the needles were inserted.

Too rapid a rate of injection of the starch suspensions might introduce considerable error. As has been pointed out in the discussion of the results obtained with dog fetuses, too rapid injection into the umbilical Vein may result in more than the normal amount of inferior vena cava blood passing through the foramen ovale to the left side of the heart.

In any series of injections where such technique was employed throughout there undoubtedly would be a constant predominance of starch found in the left heart. This occurred in the dog series only. It might likewise be assumed that too rapid injection into the superior vena cava would result in a greater quantity of starch going to the right heart.

In the present series of experiments none of the superior Vena-cava injections was made rapidly, and since there was no predominance in favor of the right heart, it seems certain that these injections were not too rapid.

Since in the dog series only, in which injection was purposely much faster than in the pig series, was there a predominance in the amount of starch found in one side of the heart, it follows that the rate of injection, if properly controlled, is not necessarily a source of great error.


Differences in the negative pressure applied to the two needles might cause the blood to be sucked by way of the foramen ovale from the side of the heart of least negative pressure to the side containing the needle of greatest negative pressure. This was overcome by the use of the Y tube connected to the two needles, as already described (p. 452). That the samples obtained simultaneously from the two sides of the heart were approximately always equal in amount is good and sufficient proof that this did not occur.

It is evident that the above objections apply chiefly to the quantitative results and, to a much less degree, to the ocular observations of the ink and starch injections.

Even though the theoretical objections to the injection method seem to have been sufficiently overcome in its practical application, fear that some might still be skeptical has led to a search for a new and more refined quantitative means of approach.

The development of the Van Slyke micro gas analysis of blood for its oxygen and carbon-dioxide content has ideally satisfied this demand. This method makes it possible to determine with chemical exactness the amount of oxygen and carbon dioxide present in the blood of the various vessels of the fetus.

The results and technique of gas analysis will appear in a separate publication. It may be stated here that the results of gas analysis have shown beyond all doubt that the starchinjection method, when properly controlled, is a reliable and practical one. While it does not possess the mathematical exactness of the gas analysis, the conclusions drawn from its results are identical with those of the latter in regard to the course of the two caval streams through the heart. 464 HOWARD B. KELLOGG

Conclusions

After injecting India ink and starch suspensions into the external jugular and umbilical veins of living pig and dog fetuses,,direct observation and quantitative determinations prove that the blood of the superior and inferior venae cavae of fetal mammals is thoroughly mixed in the right atrium and then distributed to the two ventricles.

The foramen ovale is the same relative size in the later stages of gestation as in the early ones; the fetal circulation does not approach the adult type before birth.

The early rapid development of the head, liver, and upper extremities as compared to the growth of the rest of the body does not depend upon a superior oxygen supply.

Circulatory efiiciency in the mammalian embryo apparently rests on a relatively large amount of swiftly flowing blood and upon a generous factor of safety in its oxygen.

Literature Cited

BORN, G. 1899 Beitriige zur Entwicklungsgeschichte des Saugetierherzens.

Arch. f. mik. Anat., Bd. 33, S. 368, 369.

DALTON, J. C. 1884 Doctrines of the circulation. Lea’s Son & Co., Philadelphia. -

HARVEY, W. 1628 Anatomical dissertation on the movement of the heart and blood in animals. Privately reproduced from the original edition printed at Frankfort-on-the-Main in 1628. With a translation and memoir for G. Moreton, 42 Bur-gate St., Canterbury, 1894.

HOOKER, D. R. 1921 Evidence of functional activities on the part of the capillaries and venules. Physiol. Rev., vol. 1, pp. 112-139.

KILIAN, H. F. 1826 fiber den Kreislauf des Blutes im Kinde, welches noch nicht geathmet hat. Karlsruhe, p. 200. (Loc. cit. Pohlman, 1909 b, p. 80.)

MERY 1645-1722 (Op. cit. Pohlman, 1909 b, p. 79).

POHLMAN, A. G. 1907 The circulation of the blood through the fetal heart. Johns Hopkins Hosp. Bull., vol. 18, pp. 409-412.

1909 The fetal circulation. Amer. Med., Burlington, Vt., vol. 4, pp. 317-320.

1909b The course of the blood through the heart of fetal mammale, with a note on the reptilian and amphibian circulation. Anat. Rec., vol. 3, pp. 75-109.

1916 The function of the foramen ovale. Interstate Med. Jour., vol. 23, pp. 105-124.

PREYER, W. 1883-1885 Specielle Physiologic des Embryo. Th. Griefen’s Verlag (L. Fernau), Leipzig, 8. 79-88, Tafel 5. r

REID, J. 1835 Injection of the vessels of the fetus to show some of the peculiarities of its circulation. Edinburgh Med. and Surg. Jour., vol. 43, pp. 11~13. 1835 Additional observations, Ibid., vol. 43, pp. 308—310.

SA_BA'I‘IER., RAPHAEL B. 1791 Traité complet dhénatomie, T. 2, p. 493. (Loc. cit. Pohlman, 1909b, p. 80.) SENAC’ 1773 (Op. cit. Pohlman, 1909b, p. 79.)

SERVETUS, M. 1553 Christianismi Bestitutio, p. 170. (Loc. cit. Dalton, p. 115.)

VESALIUS, ANDREAS 1543 De Humani Corporis. Liber 4, Cap. 15. (Loc. cit. Dalton, p. 108.)

WOLFF,_ C. F. 1778 De foramine ovali ejusque in dirigendo sanguinis matro. Observ. novae. Nov. comment. Scient. Petropolit 20. (Loc. cit. Pohlman, 1909b, pp. 78-80.)

ZIEGENSPECK, R. 1882 Welche Veriinderungen erffihrt die foetale Hei-zth§tig— keit regelnfalssig durch die Geburt. Inaug. diss., Jena. 1884 P1-eyer’s Physiologie des Embryo, S. 596-607. 1902 fiber Foetal Kreislauf. Miinchen. 1905 Die Lehre Von der doppelten Einmiindung der unteren Hohlvene in die Vorhofe des Herzens und der Autoritéltsglaube. Sammlung klinischer Vortrige (Ser. 14, Heft 11), No. 401.


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